Movement disorder therapy system, devices and methods, and intelligent methods of tuning

ABSTRACT

The present invention relates to methods for tuning treatment parameters in movement disorder therapy systems. The present invention further relates to a system for screening patients to determine viability as candidates for certain therapy modalities, such as deep brain stimulation (DBS). The present invention still further provides methods of quantifying movement disorders for the treatment of patients who exhibit symptoms of such movement disorders including, but not limited to, Parkinson&#39;s disease and Parkinsonism, Dystonia, Chorea, and Huntington&#39;s disease, Ataxia, Tremor and Essential Tremor, Tourette syndrome, stroke, and the like. The present invention yet further relates to methods of tuning a therapy device using objective quantified movement disorder symptom data acquired by a movement disorder diagnostic device to determine the therapy setting or parameters to be provided to the subject via his or her therapy device. The present invention also provides treatment and tuning remotely, allowing for home monitoring of subjects.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/933,078, filed on Nov. 5, 2015, and which issued as U.S. Pat. No.9,717,920 on Aug. 1, 2017, which was a continuation of U.S. patentapplication Ser. No. 13/918,948, filed on Jun. 15, 2013 and which issuedas U.S. Pat. No. 9,211,417 on Dec. 15, 2015, which was a non-provisionalapplication that claims priority to provisional U.S. Patent ApplicationSer. No. 61/698,890, which was filed on Sep. 10, 2012.

BACKGROUND OF THE INVENTION (1) Field of the Invention

The present invention relates to therapeutic medical apparatus systems,delivery systems, devices and/or methods, and to apparatus and methodsfor using neural stimulation to alleviate the symptoms of movementdisorders, such as those associated with Parkinson's disease, essentialtremor, dystonia, and Tourette's syndrome, including tremor,bradykinesia, rigidity, gait/balance disturbances, and dyskinesia, andalso for treating mental health disorders such as major depression,bipolar disorder, and obsessive compulsive disorder for example. Thepresent invention further relates to the use of a movement disorderdiagnostic device for automatically adjusting therapeutic systems,devices, delivery systems, as well as methods thereof.

(2) Technology Review

A current trend in the treatment of diseases identified as beingassociated with the central nervous system is the stimulation of targetareas of the central nervous system to affect therapeutic benefit. Suchstimulation has been accomplished with, for example, implantedelectrodes that deliver electrical stimulation to target brain regions;one class of electrical neural stimulation devices has been categorizedunder the name “deep brain stimulation” (DBS). Although the exactneurological mechanisms by which DBS therapies succeed are complex andare not yet fully understood, such therapies have proven effective intreating Parkinson's disease motor symptoms (such as tremor,bradykinesia, rigidity, and gait disturbances), and investigation intothe use of DBS for the treatment of this and other neurological andmental health disorders, including major depression,obsessive-compulsive disorder, tinnitus, obesity, criminal tendencies,and antisocial disorders, is ongoing.

Parkinson's disease (PD) affects the motor system and can becharacterized by motor symptoms including tremor, bradykinesia, andimpaired gait. When diagnosed, dopamine replacement medication isprescribed. However, over time drug effectiveness decreases, requiringincreased dosage. Frequent and stronger side effects such as dyskinesias(uncontrolled, irregular movements) and unpredictable “on”/“off”episodes are cause for more invasive intervention. Deep brainstimulation (DBS) surgery is performed when medication no longeradequately treats symptoms. Significant costs are not only associatedwith the initial implant surgeries (˜$40,000), but also subsequentstimulator battery replacements (˜$10,000-20,000), outpatientprogramming sessions (˜$1,000), and geographic disparities can put asignificant financial and emotional burden on patients over many years,especially if the expected therapeutic improvement is not achieved.Although DBS has become a standard of care for many advanced stage PDpatients, post-surgical outcomes are not equal across patients. AUniversity of Florida study followed over 100 DBS patients, primarilyPD, seeking referral to their movement disorder specialist afterexperiencing unsatisfactory improvement. Of those patients, 28% had beenmisdiagnosed presurgery and 90% had unsatisfactory symptomatic benefitincluding 40% for tremor, 37% gait, 11% for motor fluctuations anddyskinesias, and 14% for bradykinesia. The study also strongly arguesfor the need of preoperative education to ensure appropriate referraland selection of DBS candidates.

As a result, there are no set criteria for surgical patient selection.Subjective screening questionnaires have been developed to determineappropriate candidates based on a significant levodopa response (greaterthan 25%), the presence of motor fluctuations and dyskinesias, andminimal to no cognitive decline. However, methods to accurately evaluatethese criteria are severely lacking for several reasons. First, thepattern and severity of motor symptom and dyskinesias vary greatlythroughout the day. Therefore, an in-clinic assessment over multiplemedication dose cycles is not feasible and is conducted under artificialconditions. Patients are typically asked to come in OFF PD medicationsfrom the previous night. Long travel days and pain and stress associatedwith being in this therapy state may induce fatigue and increasedsymptom severity. Second, clinical rating scales, most commonly theUnified Parkinson's Disease Rating Scale (UPDRS), are used to evaluateON and OFF PD symptom states. Under the UPDRS, symptoms are subjectivelyrated on a 0-4 scale corresponding to normal, slight, mild, moderate,and severe, which can suffer from poor inter- and intra-raterreliability. An alternative, using home diaries, relies entirely on thepatient's perception of their medication state and their level ofcompliance. Patients may also underestimate dyskinesia and motor symptomseverity and have difficulty distinguishing between dyskinesia, tremor,and normal voluntary movements, a situation that can make evaluatingmedication response particularly challenging. Third, limited work hasbeen conducted to directly compare pre-surgery medication response withpost-surgery outcome in order to better select DBS candidates.

Access to movement disorder specialists to undergo the subjectivescreening questionnaires may require many clinical visits and can befinancially burdensome for the geographically disparate subset of the PDpopulation or those unable to travel. Movement disorder center locationscan limit access to well-trained clinicians and effective symptommanagement. Rural patients in one study had a significantly worsequality of life score than their urban counterparts. Telehealthtechnologies such as home monitoring and online patient data managementcan have a significant impact on the equity, accessibility, andmanagement of PD for patients who live in rural and remote communitiesor those unable to travel. In particular, one study showed that over athree-year period, telemedicine used for 100 follow-up visits for 34 PDpatients left patients and providers satisfied with use of thetechnology and their savings amounted to approximately 1500 attendanttravel hours, 100,000 travel kilometers, and $37,000 in travel andlodging costs. Typically, medication for Parkinson's disease (PD)consists of Levodopa to alleviate symptoms. Over time, however, themedication has reduced efficacy and shows increased occurrence of sideeffects such as dyskinesias. Once side effects outweigh benefits,patients consider deep brain stimulation (DBS). An electrode/wire leadis implanted in a specific location in the brain which showshyperactivity in PD patients and is sensitive to electrical stimulation.PD target sites are typically the subthalamic nucleus (STN) or globuspallidus internus (GPi). The tremor-specific target site is generallythe ventral intermedius nucleus of the thalamus (VIM). Electrical pulsescharacterized by amplitude (volts), current (amps), frequency (Hz), andpulse width (microseconds) are regulated by an implantable pulsegenerator (IPG) placed beneath the skin on the chest. Stimulationaffects motor symptoms on the contralateral side, i.e., right sidetremor will be treated on the left brain. After a patient has beenimplanted and recovered, programming sessions will fine tune stimulationsettings described above in order to minimize symptom severity, minimizeside effects, and maximize IPG battery life span. Although medication isnot eliminated, it is typically reduced significantly. DBS efficacydecreases over time as the body adjusts to stimulation and proteinbuildup around electrode lead attenuates electrical field. Programmingsessions are required throughout the patient's lifetime, though thefrequency of adjustments is typically greater at first.

A typical implanted DBS stimulation lead consists of a thin insulatedneedle comprising four platinum/iridium electrodes spaced 0.5 or 1.5 mmapart along the length of the lead. One or multiple leads may beimplanted in a target brain region or regions to providesymptom-inhibiting high-frequency stimulation, although some researchsuggests that excellent results can be achieved even when the lead isimplanted distant from a target region. A DBS lead is connected to animplantable pulse generator (IPG), which serves as a controller andpower source, via an extension cable tunneled subcutaneously to asubcutaneous pocket in the chest or abdominal cavity. The IPG typicallyincludes a battery and circuitry for telemetered communication with anexternal programming device used to adjust, or “tune,” DBS stimulationparameters, which may include but are not limited to stimulationfrequency, amplitude, pulse width (or wavelength), waveform type, andcontact configuration (that is, the selection of which electrodes areutilized from among the electrodes available on a lead, and, if two ormore electrodes are active, the relative polarity of each), and thelike. These parameters are initially set during implantation surgeryseparately and independently for each DBS lead that is implanted, andare then further fined-tuned in the outpatient clinic or in a doctor'soffice following surgery to maximize therapeutic benefit and minimizeundesirable stimulation-induced side effects. The first such programmingsession usually takes place several weeks following implantationsurgery, after the patient has recovered and inflammation at the leadplacement site has subsided.

DBS programming may be performed by movement disorder neurologists,neurosurgeons, fellows, occupational and physical therapists, nurses, oremployees of the DBS manufacturer. However, many patients haveinadequate access to DBS programming due to physicians and patientsrelocating as well as implantations occurring at facilities far from apatient's home. Additionally, there is a shortage of health careprofessionals highly trained in DBS programming. This can partially beexplained by a reluctance to participate in DBS management due to a lackof familiarly with electrophysiology or possibly the costs associatedwith postoperative DBS management. Retrospective studies found that DBSprogramming sessions take more than twice as long as typical evaluationsby movement disorder neurologists. Furthermore, programming sessionsmust be limited to 1-3 hours since longer sessions result in patientfatigue or lightheadedness. Multiple visits lead to additional travelcosts and can be particularly difficult for those traveling from ruralareas.

The approaches to programming can vary greatly across institutions.Strict iterative procedures whereby initial subjective test resultsbased on human observation are used to determine the effect theparameters have of the patient and new parameters are determined basedon those results by clinician calculation and observation are quite timeconsuming and therefore rarely followed. Many programmers make educatedguesses as to the best settings based on their prior experience;however, this experience can vary across institutions and may not takeinto account varied lead positioning. Many programmers simply ignorebipolar or tripolar configurations whereby stimulation is provided fromtwo or three contacts on a single DBS lead simultaneously, and do notadjust frequency or pulse width in an attempt to speed the programmingprocess; however, neglecting these options can lead to suboptimalpatient outcomes. Many clinician programmers do not fully appreciate thedifferent programming parameters or modes of stimulation. Inconstant-voltage IPGs, the voltage of each pulse is set, but the currentwill automatically change based on the electrode impedance. This leadsto variable amounts of current being delivered the stimulation target asimpedances change. Additionally, since impedances will vary acrosselectrode contacts, applying the same voltage on two different contactswill likely lead to different therapeutic currents being delivered. Onthe other hand, constant-current IPGs specify the current to bedelivered and adjust the voltage accordingly based on the impedance.Since the therapeutic effects of DBS are based on current delivered at agiven target, constant-current IPGs are preferable to constant-voltageIPGs.

While the above-described equipment and procedures are typical as of thefiling of this application, variations and refinements may becomecommonplace as neural implant technology advances. Conceivably, uses ofa multiplicity of DBS leads or networks of DBS leads may provide greatercoverage, enabling the stimulation of larger and more varied targetareas, and miniaturization and improved telemetry may obviate the needfor the extension cable and/or the IPG altogether as leads becomeself-powering and/or self-controlling or permit for built-in telemetry.Advances in nanotechnology and materials may also allow DBS leads in thefuture to become self-repositioning, self-cleaning, or resistant tobiological rejection for improved long-term therapeutic operation andmore precisely targeted implantation.

The current standard in evaluating the severity of movement disordersymptoms in Parkinson's disease is the manually human scored UnifiedParkinson's Disease Rating Scale (UPDRS) used to score motor tests, manyof which involve repetitive movement tasks such as touching the nose anddrawing the hand away repeatedly, or rapidly tapping the fingerstogether. A battery of exercises, typically a subset of the upperextremity motor section of the UPDRS, is normally completed during DBSlead placement surgery and subsequent programming sessions to evaluateperformance while a clinician qualitatively assesses symptoms. Each testis evaluated by a clinician based solely on visual observation andgraded on a scale that ranges from 0 (minor) to 4 (severe).

During DBS implantation surgery, various lead placement strategies areused, including inversion recovery imaging, reformatted anatomicalatlases, and formula coordinates based on known landmarks. Implantationlocation is verified and adjusted based on electrophysiological mappingusing techniques such as microelectrode recording and micro and macrostimulation. Currently, lead placement and stimulation parameters aremodified based on subjective motor examinations such as clinicalobservation such as the UPDRS motor tasks during the implantationprocedure. After lead placement, patient motor symptoms are evaluated inresponse to a set of stimulation parameters. Stimulation parameters arethen adjusted, and motor exam repeated. This trial-and-error process ofadjusting parameters and monitoring patient response is continued untilan optimal electrode position and stimulation set are established.During this programming or “tuning” process, the clinician subjectivelyassesses motor symptom improvement.

Postoperatively, assessing DBS response and reprogramming stimulationparameters require a significant time commitment. Several stimulationparameters can be modified, including electrode polarity, amplitude,current, pulse width, waveform type, and frequency. DBS programming andpatient assessment may be performed by a variety of healthcareprofessionals, including movement disorder neurologists, neurosurgeons,fellows, occupational and physical therapists, nurses, and employees ofthe DBS manufacturer. Stimulation optimization is typically performedbased on results of an exam such as the UPDRS, with the patient in fourstates (off medication/off DBS, off medication/on DBS, on medication/offDBS, and on medication/on DBS). The process of DBS adjustment isiterative and largely involves trial-and-error. Programming and patientassessment from preoperatively to one year after surgery requiresapproximately 30 hours of nursing time per patient.

Clinicians presently lack tools that combine physiological, electrical,and behavioral data to optimize electrode placement and stimulatorprogramming. Optimizing electrode placement and stimulation parametersimproves patient outcome by alleviating motor symptoms and minimizingcomplications. The present invention addresses this need for improvedelectrode placement and adjustment of deep brain stimulation parametersby providing a repeatable, automated or semi-automated tool that canassist stimulation parameter tuning during surgical electrode placementand outpatient programming sessions. In particular, the presentinvention aims to provide methods for the collection and transmission ofobjective biokinetic data during these procedures, which data is thenprocessed to output objective movement disorder symptom severitymeasures on a continuous scale in real-time to guide clinician decisionmaking. The improved resolution and repeatable results of the presentinvention should reduce time and costs of DBS procedures as well asimprove patient outcomes.

It is therefore an object of the present invention to provide a systemfor screening patients for viability of DBS therapy prior to extensive,repetitive travel and expense, and prior to requiring surgicalimplantation of DBS leads. It is further an object of the presentinventions to provide such a screening system to help minimizehealthcare costs and to prevent adverse effects in patient quality oflife associated with ineffective or unnecessary surgery, and to helpclinicians to better select courses of treatment for patients.

It is further an object of the present invention to couple at-homepatient viability screening and automatically-assigned quantitativemotor assessments with procedures and practices for DBS implantation andparameter tuning and programming in semi-automatic and automatic ways toprovide improved and less costly movement disorder patient therapy.

It is further an object of the present invention to provide automatedfunctional mapping based on objective motor assessments and algorithmsfor resolving an optimal set of programming parameters out of thethousands of possibilities to provide an expert system to enableprogramming at a local medical facility. The system is designed for useby a general practitioner or nurse rather than by a neurologist orneurophysiologist with years of experience in DBS programming anddisease management to increase access to high-quality postoperative DBSmanagement. The system will minimize the required expertise of theclinician by requiring little or no advanced knowledge of complexneurophysiology or MRI imaging.

Existing systems for quantifying Parkinson's disease motor symptoms aredescribed in this application's parent application, U.S. patentapplication Ser. No. 12/250,792, which is herein incorporated byreference, and which describes a novel system for measuring motordysfunction symptoms and computing measures based on UPDRS scorestherefrom. Preferably, the system and methods described therein areincorporated, in whole or in part, into the present invention as a meansof automatic symptom quantification. The resultant scores objectivelyquantify movement disorder symptoms advantageously using a scale that isfamiliar to clinicians.

SUMMARY OF THE INVENTION

The present invention relates to methods for semi-automatically andautomatically adjusting, or tuning, treatment parameters in movementdisorder therapy systems. Semi-automatic adjustment includes providingthe clinician, physician or technician with objective, quantitative orsemi-quantitative data or measurements related to a subject's movementdisorder symptoms, determining desired parameters, and then enteringthose parameters either semi-automatically or automatically into thesubject's therapy device. Semi-automatic or automatic adjustmentincludes providing data including but not limited to objective,quantitative or semi-quantitative data and/or measurements related to asubject's movement disorder symptoms to an algorithm, using the data ormeasurements for determining desired parameters using the algorithm, andthen entering those parameters either semi-automatically (i.e., allowingclinician, physician or technician to review and/or approve/adjust) orto automatically into the subject's therapy device. The presentinvention further relates to a system for screening patients todetermine if they are viable candidates for certain therapy modalities.The present invention still further provides methods of quantifyingmovement disorders for the treatment of patients who exhibit symptoms ofsuch movement disorders including, but not limited to, Parkinson'sdisease and Parkinsonism, Dystonia, Chorea, and Huntington's disease,Ataxia, Tremor and Essential Tremor, Tourette syndrome, and the like.The present invention yet further relates to methods of automaticallyand intelligently tuning a therapy device using objective quantifiedmovement disorder symptom data acquired by a movement disorderdiagnostic device with the therapy settings or parameters to be providedto the subject via his or her therapy device.

Objective measurement and quantification of a subject's movementdisorder symptoms, including tremor, bradykinesia, dyskinesia, gaitand/or balance disturbances, and the like requires, as a first step, ameasurement of the movement. This measurement can be performed bymeasuring a single movement metric, different movement metrics, or acombination of a number of movement metrics; and the movement metric ormetrics being measured may include linear or rotational displacement,velocity, or acceleration, or any other metric that could give aquantitative indication of motion; and the part of the body beingmeasured for motion may be a limb (as at a wrist, ankle, or finger) ormay be the trunk of the body (as at a shoulder or torso), and the head.Sensors used for measuring body movement or motion include gyroscopesand accelerometers, preferably miniaturized, electromagnets, video, amultitude of sensors or system disclosed herein, or other sensors knownto those skilled in the art. Additionally, sensors for measuringphysiological signals such as electromyogram (EMG), electrooculogram(EOG), electroencephalogram (EEG), electrocardiogram (EKG), or otherphysiological signals which can directly or indirectly measure movementmetrics in the subject may be included if such sensors and signals maybe used to sense, detect, measure, and/or quantify the subject'sexternal body motion, or related aspects. Other systems that can be usedto detect and measure body motion include motion capture systems,machine vision systems, sonic or laser Doppler velocity transducers,infrared systems, GPS, or any other system known to those skilled in theart. The movement disorder diagnostic device used in the presentinvention may incorporate one or more of any of the above sensors orsystems. Currently used movement data acquisition and diagnosticsystems, such as the one described in U.S. Pat. No. 8,187,209, hereinincorporated by reference, may similarly be used. In the presentdisclosure, “movement data” is construed as including, but not beinglimited to, any signal or set of signals, analog or digital,corresponding to movement of any part of the body or multiple parts ofthe body, independently or in conjunction with each other. This includesphysiological signals from which movement data or symptoms can bederived. Preferably, this movement data is generated with a movementsensor such as for example a gyroscope and/or an accelerometer, andadditionally or optionally a video sensor.

Movement may be continuously measured over long time spans, or may bemeasured only over a short time span, for example, as during the periodof one or more tests taken from or based on the UPDRS motor exam. Ameasurement time period comprises two separate time periods: (i) asensing time during which the movement disorder diagnostic device andits included sensors are used to sense and measure the subject'sexternal physical motion; and (ii) a processing or calculation timewherein the measured motion data is used to calculate objective scoresand/or other kinematic data that quantify the severity of the subject'smovement disorder symptoms and side effects, and wherein the scores. Themeasurement time required to adequately and accurately sense, measureand quantify the subject's movement can depend on the particularmovement test or task being performed, which typically corresponds to aparticular symptom of a movement disorder. Generally, however, thesystem aims to minimize the amount of measurement time required toobtain sufficient movement data and provide quantitative scores and/orkinematic data to continue the evaluative process. Preferably, themeasurement time required to provide objective scores and/or kinematicdata is less than about 120 minutes. More preferably, the measurementtime required to provide objective scores and/or kinematic data is lessthan about 90 minutes. Still more preferably, the measurement timerequired to provide objective scores and/or kinematic data is less thanabout 60 minutes. Yet more preferably, the measurement time required toprovide objective scores and/or kinematic data is less than about 45minutes. Even more preferably, the measurement time required to provideobjective scores and/or kinematic data is less than about 30 minutes.Still yet more preferably, the measurement time required to provideobjective scores and/or kinematic data is less than about 15 minutes.Still even more preferably, the measurement time required to provideobjective scores and/or kinematic data is less than about 10 minutes.Yet still more preferably, the measurement time required to provideobjective scores and/or kinematic data is less than about 5 minutes. Yeteven more preferably, the measurement time required to provide objectivescores and/or kinematic data is less than about 60 seconds. Even stillmore preferably, the measurement time required to provide objectivescores and/or kinematic data is less than about 30 seconds. Even yetmore preferably, the measurement time required to provide objectivescores and/or kinematic data is less than about 15 seconds. Still evenyet more preferably, the measurement time required to provide objectivescores and/or kinematic data is less than about 1 second.

In some embodiments, a periodic system may be employed wherein thesubject's external body motions are sensed, measured, and quantifiedrepeatedly but at predefined or altering intervals. In such periodicembodiments, the periodic measurements preferably conform to the abovedescribed measurement time period standards. Embodiments utilizingperiodic measurement may begin when the subject attaches or dons themovement disorder diagnostic device, and may involve a step ofinstructing the subject to attach or don the device to begin ameasurement period. Protocols for periodic measurement may be envisionedwherein a subject follows a particular schedule for measurement andquantification of movement disorder data, and wherein the schedule maychange throughout the course of treatment and/or therapy. In still otherembodiments, a continuous monitoring system may be employed wherein themovement disorder diagnostic device continuously senses, measures andquantifies the subject's external body movements over extended periodsof time, such as hours, days, weeks or months. Preferably, in thecontinuous measurement embodiments, the diagnostic device senses,measures and/or quantifies the subject's external body movementssubstantially continuously, with no breaks or stoppages in itsoperation. However, the limits of continuous operation may be defined bycharacteristics of the device, such as battery life, form factor andconstruction (e.g., if it needs to be removed to shower), and other suchconcerns.

The movement disorder diagnostic device contains at least one electroniccomponent that further may contain internal or onboard memory forstorage of the movement data such that the data may be transferred at alater time. More preferably, the movement disorder diagnostic devicefurther may contain communications electronics, which transmit themovement data to an external device for storage and/or analysis. Thecommunication electronics preferably is/are wireless, and mostpreferably is/are radio frequency wireless. The external device may be acentralized storage database, parallel databases, a cloud-baseddatabase, a computer, tablet, cell phone including for examplesmartphone, personal data assistant (PDA) or similar device, or acombination of database and computer or communication devices.Preferably, such transmission of data occurs substantially in real-time.By real-time, it is meant that preferably, data is transmitted within 30minutes of being acquired, measured, or calculated. More preferably,data is transmitted within 20 minutes of being acquired, measured, orcalculated. Still more preferably, data is transmitted within 10 minutesof being acquired, measured, or calculated. Yet more preferably, data istransmitted within 5 minutes of being acquired, measured, or calculated.Even more preferably, data is transmitted within 5 minutes of beingacquired, measured, or calculated. Still yet more preferably, data istransmitted within 3 minutes of being acquired, measured, or calculated.Even yet more preferably, data is transmitted within 60 seconds of beingacquired, measured, or calculated. Yet still more preferably, data istransmitted within 45 seconds of being acquired, measured, orcalculated. Yet even more preferably, data is transmitted within 30seconds of being acquired, measured, or calculated. Even still morepreferably, data is transmitted within 15 seconds of being acquired,measured, or calculated. Even yet more preferably, data is transmittedwithin 5 seconds of being acquired, measured, or calculated. Still evenyet more preferably, data is transmitted within 1 second of beingacquired, measured, or calculated. Yet even still more preferably, datais transmitted substantially simultaneously within milliseconds of beingacquired, measured, or calculated.

Following measurement of symptomatic movement, the next step inobjective quantification of a subject's movement disorder symptoms isthe extraction of statistical kinematic features from the acquiredmovement data via processing. This processing may take place during orfollowing data acquisition and may occur within a movement dataacquisition device or within a different processing device, such as apersonal computer, PDA, smart phone, tablet computer, touch screeninterface, or the like, with which the acquisition device interfaces,either through a cable connection or by wireless transmission. Usefulkinematic features that may be extracted from gyroscopic data mayinclude, for example, peak power angular velocity, peak power angle, RMSangular velocity, frequency, maximum amplitude, maximum peak-to-peakamplitude, mean angular velocity, and wavelet parameters, as well as thecovariance or standard deviation over time of any of these metrics.Useful kinematic features that may be extracted from accelerometer datamay include, for example, peak power acceleration, peak power velocity,peak power position, RMS acceleration, RMS velocity, RMS position,frequency, maximum amplitude, maximum peak-to-peak amplitude, meanacceleration, and wavelet parameters, as well as the covariance orstandard deviation over time of any of these metrics. In a movement dataacquisition system, or movement disorder diagnostic measuring apparatus,that combines a three-axis accelerometer and a three-axis gyroscope toproduce 6 channels of movement data, one or any combination of the abovekinematic features can be extracted from any of the 6 kinematic channelsto be used as inputs to a trained scoring algorithm in the next step.The listed kinematic features for the sensors above are intended to beexemplary, and not limiting; other types of sensors will producedifferent data from which different sets of features may be extracted.

The trained scoring algorithm used to process the kinematic featuresextracted from the movement data may comprise, for example, one or moreof a simple or multiple linear regression, an artificial neural network,a Bayesian network, or a genetic algorithm. The output of the trainedscoring algorithm may be a single score or multiple scores of any scale;a single score on the same scale as that of the UPDRS may be preferredin certain applications where simplicity or familiarity is the paramountconcern, while more sophisticated scores and scales may be preferred forother advanced applications, such as those that involve recommendationsfor treatment or closed-loop automated treatment delivery.

In various embodiments, following the step of symptom quantification, aseparate tuning algorithm may compute suggested changes to the therapysystem parameter settings based on the result of the symptomquantification algorithm and known or predicted current therapy systemparameter settings and physiological models.

Depending on the embodiment of the invention, the current therapy systemparameter settings changes may be input into the algorithm by a softwareuser interface (integrated tuning), or may be automatically sensed andinput from the DBS parameter settings by communicating with a DBSimplant or its programmer device or unit (intelligent tuning), or may beknown because the DBS parameter settings have been preset to some knownbaseline settings or restored to a previously saved settings preset. Theexisting parameter settings might also be predicted or derived based,for example, on observed or measured therapy effectiveness. Suggestedtherapy system parameter settings changes are then input into thetherapy system, and their effectiveness is measured using theabove-described method of symptom quantification.

The process of tuning therapy system parameter settings may remainiterative, but the present invention significantly minimizes, or atleast greatly reduces the time and expertise required to arrive atoptimized stimulation or therapy parameter settings, advantageouslyallowing clinicians, technicians or physicians with lesser training orexperience to adjust parameter settings during patient visits, and to doso in less time than is currently required. Additionally, the presentinvention increases access to geographically disparate populations byputting the expertise into the system and reducing or eliminating theneed for an expert or trained clinician to be present with each subject.

Many embodiments of the present invention include optimization or tuningalgorithm(s) which are used to determine or recommend optimum therapysettings or parameters. Such optimization algorithms may include, butare not limited to simplex algorithms, extensions of the simplexalgorithm designed for quadratic and/or linear function programming,combinatorial algorithms, and other multi-variant optimizationalgorithms known to those in the art. In order to determine what adesired or optimal level of therapy parameters might be, the subject'ssymptoms or side effects must first be measured and quantified. Themeasurement and quantification preferably take place while the subjectis performing at least one movement disorder test as instructed. Oncethe initial measurement and quantification has been obtained, the systemand/or, in some embodiments a clinician, physician or technician,programs a second level of therapy parameters into the subject's therapydevice, and the subject repeats the movement disorder test(s) while thesymptoms or side effects are again measured and quantified. This processis repeated until the desired result(s), goals or constraints areachieved. These processes and steps are described in greater detailbelow. Preferably, whether obtaining optimized therapy parameters orsettings, or when iteratively testing to determine a second level oftherapy parameters, preferably, the subject is instructed to perform,and performs, at least 1 movement disorder test, where the testcomprises at least one task related to the subject's external bodymotion. More preferably, the subject is instructed to perform, andperforms, at least 2 movement disorder tests. Still more preferably, thesubject is instructed to perform, and performs, at least 3 movementdisorder tests. Yet more preferably, the subject is instructed toperform, and performs, at least 4 movement disorder tests. Even morepreferably, the subject is instructed to perform, and performs, at least5 movement disorder tests. Still yet more preferably, the subject isinstructed to perform, and performs, at least 6 movement disorder tests.Even still more preferably, the subject is instructed to perform, andperforms, at least 7 movement disorder tests.

Optimization of stimulation or therapy parameters or settings can bedescribed in reference to various constraints or desired results. Insome embodiments, optimization, or the level of parameters or settingselected based at least in part on movement disorder tests, results andscores refers to a reduction or minimization of symptom occurrenceand/or severity. Preferably in such embodiments, an optimized or secondlevel of therapy parameters or settings corresponds to at least a 10%reduction in the occurrence and/or severity of the subject's symptomswhile the subject is receiving therapy or is under the effects ofrecently received therapy. More preferably, an optimized or second levelof therapy parameters or settings corresponds to at least a 20%reduction in the occurrence and/or severity of the subject's symptomswhile the subject is receiving therapy or is under the effects ofrecently received therapy. Yet more preferably, an optimized or secondlevel of therapy parameters or settings corresponds to at least a 30%reduction in the occurrence and/or severity of the subject's symptomswhile the subject is receiving therapy or is under the effects ofrecently received therapy. Still more preferably, an optimized or secondlevel of therapy parameters or settings corresponds to at least a 40%reduction in the occurrence and/or severity of the subject's symptomswhile the subject is receiving therapy or is under the effects ofrecently received therapy. Even more preferably, an optimized or secondlevel of therapy parameters or settings corresponds to at least a 50%reduction in the occurrence and/or severity of the subject's symptomswhile the subject is receiving therapy or is under the effects ofrecently received therapy. Still yet more preferably, an optimized orsecond level of therapy parameters or settings corresponds to at least a60% reduction in the occurrence and/or severity of the subject'ssymptoms while the subject is receiving therapy or is under the effectsof recently received therapy. Even yet more preferably, an optimized orsecond level of therapy parameters or settings corresponds to at least a70% reduction in the occurrence and/or severity of the subject'ssymptoms while the subject is receiving therapy or is under the effectsof recently received therapy. Yet still more preferably, an optimized orsecond level of therapy parameters or settings corresponds to at least a75% reduction in the occurrence and/or severity of the subject'ssymptoms while the subject is receiving therapy or is under the effectsof recently received therapy. Even still more preferably, an optimizedor second level of therapy parameters or settings corresponds to atleast an 80% reduction in the occurrence and/or severity of thesubject's symptoms while the subject is receiving therapy or is underthe effects of recently received therapy. Yet even more preferably, anoptimized or second level of therapy parameters or settings correspondsto at least an 85% reduction in the occurrence and/or severity of thesubject's symptoms while the subject is receiving therapy or is underthe effects of recently received therapy. Still even more preferably, anoptimized or second level of therapy parameters or settings correspondsto at least a 90% reduction in the occurrence and/or severity of thesubject's symptoms while the subject is receiving therapy or is underthe effects of recently received therapy. Yet still even morepreferably, an optimized or second level of therapy parameters orsettings corresponds to at least a 95% reduction in the occurrenceand/or severity of the subject's symptoms while the subject is receivingtherapy or is under the effects of recently received therapy. Mostpreferably, an optimized or second level of therapy parameters orsettings corresponds to substantially eliminating the occurrence and/orseverity of the subject's symptoms while the subject is receivingtherapy or is under the effects of recently received therapy.

In other embodiments, optimization, or the level of parameters orsetting selected based at least in part on movement disorder tests,results and scores refers to a reduction or minimization of side effectoccurrence and or severity. Side effects may be a result ofpharmaceutical therapy (medication) the subject is receiving to treathis or her movement disorders, or from the stimulation therapy (e.g.,DBS). Preferably in such embodiments, an optimized or second level oftherapy parameters or settings corresponds to at least a 10% reductionin the occurrence and/or severity of the subject's side effects whilethe subject is receiving therapy or is under the effects of recentlyreceived therapy. More preferably, an optimized or second level oftherapy parameters or settings corresponds to at least a 20% reductionin the occurrence and/or severity of the subject's side effects whilethe subject is receiving therapy or is under the effects of recentlyreceived therapy. Yet more preferably, an optimized or second level oftherapy parameters or settings corresponds to at least a 30% reductionin the occurrence and/or severity of the subject's side effects whilethe subject is receiving therapy or is under the effects of recentlyreceived therapy. Still more preferably, an optimized or second level oftherapy parameters or settings corresponds to at least a 40% reductionin the occurrence and/or severity of the subject's side effects whilethe subject is receiving therapy or is under the effects of recentlyreceived therapy. Even more preferably, an optimized or second level oftherapy parameters or settings corresponds to at least a 50% reductionin the occurrence and/or severity of the subject's side effects whilethe subject is receiving therapy or is under the effects of recentlyreceived therapy. Still yet more preferably, an optimized or secondlevel of therapy parameters or settings corresponds to at least a 60%reduction in the occurrence and/or severity of the subject's sideeffects while the subject is receiving therapy or is under the effectsof recently received therapy. Even yet more preferably, an optimized orsecond level of therapy parameters or settings corresponds to at least a70% reduction in the occurrence and/or severity of the subject's sideeffects while the subject is receiving therapy or is under the effectsof recently received therapy. Yet still more preferably, an optimized orsecond level of therapy parameters or settings corresponds to at least a75% reduction in the occurrence and/or severity of the subject's sideeffects while the subject is receiving therapy or is under the effectsof recently received therapy. Even still more preferably, an optimizedor second level of therapy parameters or settings corresponds to atleast an 80% reduction in the occurrence and/or severity of thesubject's side effects while the subject is receiving therapy or isunder the effects of recently received therapy. Yet even morepreferably, an optimized or second level of therapy parameters orsettings corresponds to at least an 85% reduction in the occurrenceand/or severity of the subject's side effects while the subject isreceiving therapy or is under the effects of recently received therapy.Still even more preferably, an optimized or second level of therapyparameters or settings corresponds to at least a 90% reduction in theoccurrence and/or severity of the subject's side effects while thesubject is receiving therapy or is under the effects of recentlyreceived therapy. Yet still even more preferably, an optimized or secondlevel of therapy parameters or settings corresponds to at least a 95%reduction in the occurrence and/or severity of the subject's sideeffects while the subject is receiving therapy or is under the effectsof recently received therapy. Most preferably, an optimized or secondlevel of therapy parameters or settings corresponds to substantiallyeliminating the occurrence and/or severity of the subject's side effectswhile the subject is receiving therapy or is under the effects ofrecently received therapy.

Preferably, where the desired result is to reduce or minimize thesubject's movement disorder symptoms, the optimized or second level oftherapy parameters results in a reduction or minimization of at least 1movement disorder symptom. More preferably, the optimized or secondlevel of therapy parameters results in a reduction or minimization of atleast 2 movement disorder symptoms. Still more preferably, the optimizedor second level of therapy parameters results in a reduction orminimization of at least 3 movement disorder symptoms. Yet morepreferably, the optimized or second level of therapy parameters resultsin a reduction or minimization of at least 4 movement disorder symptoms.Even more preferably, the optimized or second level of therapyparameters results in a reduction or minimization of at least 5 movementdisorder symptoms.

Preferably, where the desired result is to reduce or minimize thesubject's side effects from medication or therapy, the optimized orsecond level of therapy parameters results in a reduction orminimization of at least 1 side effect. More preferably, the optimizedor second level of therapy parameters results in a reduction orminimization of at least 2 side effects. Still more preferably, theoptimized or second level of therapy parameters results in a reductionor minimization of at least 3 side effects. Yet more preferably, theoptimized or second level of therapy parameters results in a reductionor minimization of at least 4 side effects. Even more preferably, theoptimized or second level of therapy parameters results in a reductionor minimization of at least 5 side effects.

Other secondary constraints or desired results may also be consideredwhen optimizing or determining a second level of therapy parameters orsettings such as maximizing the battery life of the therapeutic (e.g.,DBS) device, maximizing the therapeutic window, and the like. Suchconstraints or desired results as these are secondary only in that theprimary goal of the therapy is to increase the subject's quality of lifeby reducing or minimizing symptoms or side effects, or balancing both,while also trying to improve the duration and quality of therapyotherwise. For example, maximizing battery life of the therapy devicehelps to increase the time required between subject's visits to theclinician, physician or technician as well as ensuring that the devicehas sufficient power and capability to effectively provide thedetermined levels of therapy. Similarly with maximizing the therapeuticwindow, which also increases the time between visits, but also maximizesthe length of time that the stimulation therapy has a positive effect onthe subject and reducing the number of stimulations required to achievethe desired results. Typically, the subject and his or her clinician,physician or technician will agree upon the primary desired result, suchas minimizing symptoms, but numerous other such constraints will also beconsidered, weighed and balanced in determining the optimized or secondlevel of parameters or settings.

Several embodiments may include a general optimization strategy in whichcombinations of the above desired results or constraints are used toselect the appropriate optimized settings. For example, such embodimentsmay optimize based on reducing or minimizing both symptoms and sideeffects. Any combination of type and/or number of desired results orconstraints may be used to optimize the system. Preferably, at least twodifferent desired results or constraints are considered when determiningan optimized group of therapy settings or parameters. More preferably,at least three different desired results or constraints are consideredwhen determining an optimized group of therapy settings or parameters.Still more preferably, at least four different desired results orconstraints are considered when determining an optimized group oftherapy settings or parameters. Yet more preferably, at least fivedifferent desired results or constraints are considered when determiningan optimized group of therapy settings or parameters. Even morepreferably, at least six different desired results or constraints areconsidered when determining an optimized group of therapy settings orparameters. Most preferably, more than seven different desired resultsor constraints are considered when determining an optimized group oftherapy settings or parameters.

Numerous embodiments of the present invention are envisioned in thisdisclosure. These following embodiments are examples of the manyembodiments encompassed by the present invention, but do not in any waylimit the many other embodiments covered by this disclosure.

One embodiment of the present invention includes a method of tuning amovement disorder therapy system comprising steps of providing amovement disorder diagnostic device to a subject having a deep brainstimulation (DBS) device with a first level of DBS parameters, themovement disorder diagnostic device comprising at least onephysiological or movement sensor having a signal, and a processorcomprising an algorithm, instructing the subject to perform at least onemovement disorder test(s) while the subject is undergoing DBS therapy oris under the effects of DBS therapy, measuring and quantifying motorsymptoms of the subject based at least in part on the signal from the atleast one physiological or movement sensor(s) during the at least onemovement disorder test(s), entering data corresponding to the subject'smeasured and quantified motor symptoms into an algorithm, providing,with the algorithm, a second level of DBS parameters based at least inpart on the data entered into the algorithm, and entering the secondlevel of DBS parameters into the subject's DBS device such that thesubject's DBS device operates under the second level of DBS parameters.

Another embodiment of the present invention includes a method of tuninga movement disorder therapy system comprising steps of providing amovement disorder diagnostic device to a subject having a deep brainstimulation (DBS) device with a first level of DBS parameters, themovement disorder diagnostic device comprising at least onephysiological or movement sensor having a signal, and a processorcomprising an algorithm, instructing the subject to perform at least onemovement disorder test(s) while the subject is undergoing DBS therapy oris under the effects of DBS therapy, measuring and quantifying motorsymptoms of the subject based at least in part on the signal from the atleast one physiological or movement sensor(s) during the at least onemovement disorder test(s), entering data corresponding to the subject'smeasured and quantified motor symptoms into an algorithm, determining,with the algorithm, at least two optional groups of DBS parameters, eachoptional group of parameters corresponding to a different desiredoutcome or constraint, selecting one of the at least two optional groupsof DBS parameters, and entering the selected optional group of DBSparameters into the subject's DBS device such that the subject's DBSdevice operates under the second level of DBS parameters.

Still another embodiment of the present invention includes a method oftuning a movement disorder therapy system comprising steps of providinga movement disorder diagnostic device to a subject having a deep brainstimulation (DBS) device with a first level of DBS parameters, themovement disorder diagnostic device comprising at least onephysiological or movement sensor having a signal, and a processorcomprising an algorithm, instructing the subject to perform at least onemovement disorder test(s) while the subject is undergoing DBS therapy oris under the effects of DBS therapy, measuring and quantifying motorsymptoms of the subject based at least in part on the signal from the atleast one physiological or movement sensor(s) during the at least onemovement disorder test(s), entering data corresponding to the subject'smeasured and quantified motor symptoms into an algorithm, determining,with the algorithm, at least two optional groups of DBS parameters, eachoptional group of parameters corresponding to a different desiredoutcome or constraint, selecting at least two of the at least twooptional groups of DBS parameters, combining the at least two selectedoptional groups of DBS parameters into one set of combined DBSparameters, and entering the combined group of DBS parameters into thesubject's DBS device such that the subject's DBS device operates underthe second level of DBS parameters.

A method of tuning a movement disorder therapy system comprising stepsof providing a movement disorder diagnostic device to a subject having adeep brain stimulation (DBS) device with a first level of DBSparameters, the movement disorder diagnostic device comprising at leastone physiological or movement sensor having a signal, and a processorcomprising an algorithm, instructing the subject to perform at least onemovement disorder test(s) while the subject is undergoing DBS therapy oris under the effects of DBS therapy, measuring and quantifying motorsymptoms of the subject based at least in part on the signal from the atleast one physiological or movement sensor(s) during the at least onemovement disorder test(s), entering data corresponding to the subject'smeasured and quantified motor symptoms into an algorithm, providing,with the algorithm, a second level of DBS parameters based at least inpart on the data entered into the algorithm, and uploading,substantially simultaneously with transmitting, with at least oneelectronic component the second level of DBS parameters and/or measuredand quantified motor symptoms to a database for storage and/or review bya clinician, technician or physician.

A method of tuning a movement disorder therapy system comprising stepsof providing a movement disorder diagnostic device to a subject having adeep brain stimulation (DBS) device with a first level of DBSparameters, the movement disorder diagnostic device comprising at leastone physiological or movement sensor having a signal, and a processorcomprising an algorithm, instructing the subject to perform at least onemovement disorder test(s) while the subject is undergoing DBS therapy oris under the effects of DBS therapy, measuring and quantifying motorsymptoms of the subject based at least in part on the signal from the atleast one physiological or movement sensor(s) during the at least onemovement disorder test(s), entering data corresponding to the subject'smeasured and quantified motor symptoms into an algorithm, determining,with the algorithm, at least two optional groups of DBS parameters, eachoptional group of parameters corresponding to a different desiredoutcome or constraint, selecting one of the at least two optional groupsof DBS parameters, and uploading, substantially simultaneously withtransmitting, with at least one electronic component the second level ofDBS parameters and/or measured and quantified motor symptoms to adatabase for storage and/or review by a clinician, technician orphysician.

A method of tuning a movement disorder therapy system comprising stepsof providing a movement disorder diagnostic device to a subject having adeep brain stimulation (DBS) device with a first level of DBSparameters, the movement disorder diagnostic device comprising at leastone physiological or movement sensor having a signal, and a processorcomprising an algorithm, instructing the subject to perform at least onemovement disorder test(s) while the subject is undergoing DBS therapy oris under the effects of DBS therapy, measuring and quantifying motorsymptoms of the subject based at least in part on the signal from the atleast one physiological or movement sensor(s) during the at least onemovement disorder test(s), entering data corresponding to the subject'smeasured and quantified motor symptoms into an algorithm, determining,with the algorithm, at least two optional groups of DBS parameters, eachoptional group of parameters corresponding to a different desiredoutcome or constraint, selecting at least two of the at least twooptional groups of DBS parameters, combining the at least two selectedoptional groups of DBS parameters into one set of combined DBSparameters, and uploading, substantially simultaneously withtransmitting, with at least one electronic component the second level ofDBS parameters and/or measured and quantified motor symptoms to adatabase for storage and/or review by a clinician, technician orphysician.

A method of tuning a movement disorder therapy system comprising stepsof providing a movement disorder diagnostic device to a subject having adeep brain stimulation (DBS) device with a first level of DBSparameters, the movement disorder diagnostic device comprising at leastone physiological or movement sensor having a signal, and a processorcomprising an algorithm, displaying on a programming device a list ofactivities, actions or tasks for the subject to select from, having thesubject elect at least one activity, action or task from the list on theprogramming device, selecting with the movement disorder diagnosticdevice a predetermined set of DBS parameters corresponding to theelected at least one activity, action or task, and entering with theprogramming device the group of selected DBS parameters corresponding tothe at least one elected activity, action or task into the subject's DBSdevice such that the subject's DBS device operates under the selectedgroup of DBS parameters while the subject performs the at least oneelected activity, action, or task.

A method of tuning a movement disorder therapy system comprising stepsof providing a movement disorder diagnostic device to a subject having adeep brain stimulation (DBS) device with a first level of DBSparameters, the movement disorder diagnostic device comprising at leastone physiological or movement sensor having a signal, and a processorcomprising an algorithm, displaying on a programming device a list ofactivities, actions or tasks for the subject to select from, having thesubject elect at least one activity, action or task from the list on theprogramming device, selecting with the movement disorder diagnosticdevice a predetermined set of DBS parameters corresponding to theelected at least one activity, action or task, entering with theprogramming device the group of selected DBS parameters corresponding tothe at least one elected activity, action or task into the subject's DBSdevice such that the subject's DBS device operates under the selectedgroup of DBS parameters, measuring and quantifying motor symptoms of thesubject based at least in part on the signal from the at least onephysiological or movement sensor(s) while the subject performs the atleast one elected activity, action or task, entering data correspondingto the subject's measured and quantified motor symptoms into analgorithm, providing, with the algorithm, a second level of DBSparameters based at least in part on the data entered into thealgorithm, the second level of DBS parameters maximizing the subject'sability to perform the at least one elected activity, action or task,and entering the second level of DBS parameters into the subject's DBSdevice such that the subject's DBS device operates under the secondlevel of DBS parameters while the subject performs the at least oneelected activity, action or task.

It is to be understood that both the foregoing general description andthe following detailed description are merely exemplary of theinvention, and are intended to provide an overview or framework forunderstanding the nature and character of the invention as it isclaimed. The accompanying drawings are included to provide a furtherunderstanding of the invention, and are incorporated in and constitute apart of this specification. The drawings illustrate various embodimentsof the invention and together with the description serve to explain theprinciples and operation of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Schematic view of a subject undergoing post-surgical DBSadjustment with one embodiment of the invention involving automatedinstruction of the subject and is electronic transmission between thesystem and the subject's DBS device.

FIG. 2. Schematic view of a subject undergoing post-surgical DBSadjustment with another embodiment of the invention involving electronictransmission between the system and the subject's DBS device.

FIG. 3. Flow diagram of a parameter adjustment suggestion algorithm insome embodiments of the present invention.

FIG. 4. Flow diagram of an artificial neural network of the parameteradjustment suggestion algorithm in some embodiments of the presentinvention.

FIG. 5. Graphic depiction of display pages displaying test results andscores, one embodiment of a tuning map, as well as one embodiment of aparameter input screen.

FIG. 6. Graphic depiction of one embodiment of tuning maps used todisplay test results and symptom severity objectively measured by thesystem and displayed as a scatter plot of symptom severity scores.

FIG. 7. Illustration of the subject screening process to determine ifDBS is a viable option for a particular subject.

FIG. 8. Illustration of various embodiments of the DBS parameterprogramming/tuning process.

FIG. 9. Illustration depicting the ability of bipolar stimulation toshape the electrical stimulation field to avoid activating a side effectregion of the brain as opposed to monopolar stimulation which does notallow shaping of the electrical field.

FIG. 10. One embodiment of an interface device allowing a user to selectan activity to perform, and which can change the subject's therapyparameters or settings based on the selected activity.

FIG. 11. Flow chart describing one embodiment of the present inventionwherein a subject's therapy device is intelligently and automaticallyprogrammed with updated parameters or settings, and where the updatedparameters or settings are determined by an algorithm(s) based onmeasured and quantified motor symptom data.

FIG. 12. Flow chart describing one embodiment of the present inventionwherein a subject's therapy device is intelligently and automaticallyprogrammed with updated parameters or settings, where an algorithmprovides at least two optional sets of parameters or settings and thesubject selects one of the groups based on a particular activity inwhich he or she wishes to engage.

FIG. 13. Flow chart describing one embodiment of the present inventionwherein a subject's therapy device is intelligently and automaticallyprogrammed with updated parameters or settings, where an algorithmprovides at least two optional sets of parameters or settings and thesubject selects at least two of the groups based on a particularactivity in which he or she wishes to engage, and the groups arecombined and optimized to best meet the combined needs of the subject.

FIG. 14. Flow chart describing one programming option embodiment of thepresent invention wherein an algorithm(s) provides a recommended set ofparameters or settings to be reviewed and approved before thoseparameters or settings are programmed into the subject's therapy device.

FIG. 15. Flow chart depicting a start-to-finish description of theprocess from the subject exhibiting movement disorder symptoms throughtreatment and therapy of those movement disorder symptoms, and where thesubject's therapy device is programmed automatedly and intelligentlyusing an algorithm to determine optimal therapy parameters or settings.

FIG. 16. Flow chart of one exemplary embodiment of an intelligent tuningalgorithm for determining or selecting a second set or group of therapyparameters or settings based on measured and quantified movement dataand/or movement disorder and various constraints.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to methods for semi-automatically andautomatically adjusting, or tuning, treatment parameters in movementdisorder therapy systems. Semi-automatic adjustment includes providingthe clinician, physician or technician with objective, quantitative orsemi-quantitative data or measurements related to a subject's movementdisorder symptoms, determining desired parameters, and then enteringthose parameters either semi-automatically or automatically into thesubject's device. Semi-automatic and automatic adjustment includesproviding objective, quantitative or semi-quantitative data ormeasurements related to a subject's movement disorder symptoms to analgorithm, determining desired parameters using the algorithm, and thenentering those parameters either semi-automatically (i.e., allowingclinician, physician or technician review) or automatically into thesubject's therapy device. The present invention further relates to asystem for screening patients to determine if they are viable candidatesfor certain therapy modalities. The present invention still furtherprovides methods of quantifying movement disorders for the treatment ofpatients who exhibit symptoms of such movement disorders including, butnot limited to, Parkinson's disease and Parkinsonism, Dystonia, Chorea,and Huntington's disease, Ataxia, Tremor and Essential Tremor, Tourettesyndrome, stroke, and the like. The present invention yet furtherrelates to methods of automatically and intelligently tuning a therapydevice using objective quantified movement disorder symptom dataacquired by a movement disorder diagnostic device with the therapysetting or parameters to be provided to the subject via his or hertherapy device.

The movement disorder diagnostic device, systems and/or methods of thevarious embodiments of the present invention are used to screenpatients, analyze, score, and treat various disorders, and especiallymovement disorders and mental health disorders. Movement disorders forpurposes of this application include but are not limited to Parkinson'sdisease and Parkinsonism, Dystonia, Chorea, and Huntington's disease,Ataxia, Tremor and Essential Tremor, Tourette syndrome, stroke, and thelike. Mental health disorders include, but are not limited to majordepression, bipolar disorder, obsessive compulsive disorder, andantisocial disorders. Some of the treatments used for these disordersinvolve pharmaceutical interventions, fetal cell transplants, surgery,or deep brain stimulation. The efficacy of an intervention is oftenjudged by the intervention's ability to alleviate subject symptoms andimprove subject quality of life. The subject on which the system ormethod is used is a human or another form of animal.

The movement disorder diagnostic device the various embodiments of thepresent invention are preferably portable. By portable it is meant amongother things that the device is capable of being transported relativelyeasily. Relative ease in transport means that the device can be carriedby a single person, generally in a carrying case to the point of use orapplication. Additionally, relative ease in transport means that thedevice is easily worn, carried by or attached to a subject. Furthermorethe device preferably should be relatively light-weight. By relativelylightweight, preferably the device weighs less than about 3 lbs., morepreferably less than about 2 lbs., even more preferably less than about1 lb., still more preferably less than about 0.5 lbs., still preferablyless than about 2 ounces and most preferably less than 0.5 ounces. Bybeing lightweight and further compact, the device should gain greateracceptance for use by the subject. The system for measuring andcalculating the severity of the symptoms including external computerspreferably weighs less than about 15 lbs., more preferably less thanabout 10 lbs., still more preferably less than about 5 lbs., even morepreferably less than about 2 lbs., and most preferably less than 0.5lbs. This system more preferably can fit in a reasonably sized carryingcase so the patient or their caregiver can easily transport the system.

Another advantage of the systems and methods of the present invention isthe ability to determine or calculate the severity of a subject'ssymptoms in real time. Throughout this disclosure, by real time it ismeant that within 30 minutes of sensing and measurement the severity ofa subject's symptoms can be calculated or determined. Real time, morepreferably means that the subject's symptoms can be calculated ordetermined in less than about 30 seconds, more preferably in less thanabout 1 second, even more preferably in less than about 0.1 seconds, andmost preferably in less than about 0.01 seconds.

The devices of the various embodiments of the present invention can formpart of a system for use by a physician, veterinarian, technician orclinician for analysis or evaluation of a subject's movement disorder;for pharmaceutical research, for adjustment of neurostimulation therapysuch as for example deep brain stimulation (DBS) or spinal cordstimulation (SCS), or for delivery of pharmaceutical compounds. Otherelements of this system may include but are not limited to receivers,routers, communication devices, processors, displays, drug deliverydevices and the like, some of which are described further in variousembodiments described in more detail below.

The movement disorder diagnostic device, described in greater detailbelow, worn, carried by or attached to the subject, contains variousphysiological or movement sensor(s) used to measure the subject'sexternal body motion and/or other physiological signals from thesubject's body. The movement disorder diagnostic device may temporarilystore the subject's movement or physiological data in onboard memoryand/or transmit this data to an external device. In some embodiments,the movement disorder diagnostic device may directly transmit the datato a centralized database, to multiple databases at the same or multiplelocations, or to a cloud-based database where the data can be stored andaccessed essentially immediately by authorized users who can analyzeand/or further process the data, use it to diagnose or assess thesubject's symptoms or disorders, or the like. Additionally, oralternatively, the movement disorder diagnostic device can transmit themovement or physiological data to an external computer device. Thecomputer device, though called a tablet herein, is understood to be anytype of device known to those skilled in the art usable for the intendedpurpose(s) or function(s), including, but not limited to, desktopcomputers, laptop computers, tablet computers, personal digitalassistants (PDAs, “smart” cellular telephones, and the like). Thecomputer device, or tablet, may be provided as part of the presentinvention's system, but in many embodiments the movement disorderdiagnostic device is designed to work with and communicate with suchdevices of any third-party manufacturer or provider who provides suchdevices for the intended function or purpose of the present invention.In such cases, a software installation providing the user interface,tuning map capabilities, diagnostic and analysis tools, and the likewould simply be installed on the third-party computer device or tabletas software or an application (or “app”), or the interaction with theuser(s) can be web based through a web portal. The tuning map is a toolthat allows the clinician, physician or technician to review and/ordetermine the next, or preferably best (optimized) therapeutic settingsor parameters for the subject's therapy device, such as a DBS device. Inthe present invention, tuning maps are used primarily as a tool forreview and analysis of the automatically, intelligently generatedparameters or settings provided by a tuning algorithm, and not forfull-time or regular interaction and programming by a clinician,physician or technician. The tuning maps are described in greater detailin U.S. patent application Ser. Nos. 13/861,790 and 13/153,063, both ofwhich are herein incorporated by reference. Once the next therapyparameters or settings have been determined, a programmer device or unitcan be used to communicate directly with the therapy device. Again, theprogrammer device or unit may be integrated into the subject-worndiagnostic device, a separate unit in and of itself, or may be part ofthe tablet or computer, and automatically communicates the parameters orsettings to the programmer device or unit or directly to the subject'stherapy device.

As noted, various embodiments of the present invention may include asensor for measuring a subject's external body motion. The invention mayalso include at least one sensor for indirectly measuring movementmetrics. Many types of sensors are known by those skilled in the art formeasuring external body motion or providing physiological signalsthrough which body movement information may be derived. External bodymotion sensors include but are not limited to accelerometers,gyroscopes, magnetometers, resistive bend sensors, combinations thereof,and the like. Preferably, a combination using at least an accelerometerand gyroscope is used. Sensors through which body movement informationmay be derived include, but are not limited to, electromyogram (EMG),electrooculogram (EOG), electroencephalogram (EEG), electrocardiogram(EKG), or other physiological signals which can directly or indirectlymeasure movement metrics in the subject may be included if such sensorsand signals may be used to sense, detect, measure, and/or quantify thesubject's external body motion, or related aspects.

In embodiments where a gyroscope is a sensor of the present invention,the gyroscope functions on the principle of the Coriolis Effect and acapacitive-based sensing system. Rotation of the sensor causes a shiftin response of an oscillating silicon structure resulting in a change incapacitance. A typical application specific integrated circuit (ASIC),manufactured using a standard complementary metal oxide semiconductor(CMOS) manufacturing process, detects and transforms changes incapacitance into an analog output voltage, which is proportional toangular rate. The sensor element design utilizes differential capacitorsand symmetry to significantly reduce errors from acceleration andoff-axis rotations.

In embodiments where an accelerometer is a sensor of the presentinvention, it may optionally be a dual axis acceleration measurementsystem on a single monolithic integrated circuit (IC). Such embodimentsmay contain a polysilicon surface-micromachined sensor and signalconditioning circuitry to implement open-loop acceleration measurementarchitecture. For each axis an output circuit converts the analog signalto a duty cycle modulated (DCM) digital signal that can be decoded witha counter/timer port on a microprocessor. The dual axis accelerometer iscapable of measuring both positive and negative accelerations. Thesensor may be a surface micromachined polysilicon structure built on topof the silicon wafer. Polysilicon springs suspend the structure over thesurface of the wafer and provide a resistance against accelerationforces. Deflection of the structure is measured using a differentialcapacitor that consists of independent fixed plates and central platesattached to the moving mass. The fixed plates are driven by 180-degreeout of phase square waves. Acceleration will deflect the beam andunbalance the differential capacitor, resulting in an output square wavewhose amplitude is proportional to acceleration. Phase sensitivedemodulation techniques are then used to rectify the signal anddetermine the direction of the acceleration. The output of thedemodulator drives a duty cycle modulator (DCM) stage through a 32 kOhmresistor. At this point a pin is available on each channel to allow theuser to set the signal bandwidth of the device by adding a capacitor.This filtering improves measurement resolution and helps preventaliasing. After being low-pass filtered, the analog signal is convertedto a duty cycle modulated signal by the DCM stage. A single resistorsets the period for a complete cycle (T2). A 0 g acceleration produces anominally 50% duty cycle. The acceleration signal can be determined bymeasuring the length of the T1 and T2 pulses with a counter/timer orwith a polling loop using a low cost microcontroller.

In preferred embodiments, a single sensor unit comprising at least anaccelerometer and a gyroscope may be used. More preferably, a singlechip containing both a 3-axis accelerometer and a 3-axis gyroscope(e.g., Invensense MPU-6000), may be used. The sensor unit preferably notonly comprises at least an accelerometer and a gyroscope, but alsoallows for integration of other sensors external to the sensor unit.Preferably, the accelerometer and gyroscope are each three-axis sensorscapable of measuring their respective movements (acceleration andorientation) in each of the three dimensions of movement (X, Y and Z).Each of the accelerometer and gyroscope may output a separate signal fortheir respective measurements in each axis, and these signals are allconverted from analog to digital by a bank of analog-to-digitalconverters (ADC). The separate ADCs for each axis of the accelerometerand gyroscope allow for simultaneous sampling of each sensor andeliminate the need for an external multiplexer. Preferably the sensorunit as a whole, and the accelerometer and gyroscope in particular arecapable of operation with low power consumption. Preferably; theaccelerometer and gyroscope are user-programmable such that the user maydefine an operating range in which the sensors will work (e.g., theaccelerometer may be programmed to operate from as low as ±2 g to ashigh as ±16 g, and the gyroscope from as low as ±250 degrees/second toas high as ±2000 degrees/second). Some embodiments may include othersensors integrated into the sensor unit as well, for example, atemperature sensor which may be used to monitor the temperature of thesensor unit and ensure it is operating properly and under safeconditions.

The sensor unit further preferably comprises a digital motion processor(DMP) which may perform some preprocessing or processing of the sensorsignals using motion-related algorithms. The digital motion processor atleast preprocesses and/or processes the accelerometer and gyroscopesignals to begin the analysis of the signals and to decrease theprocessing load on the external processor. Many embodiments may includeexternal or additional sensors that are not housed within the sensorunit, but whose signals are transmitted to the sensor unit forintegration with the accelerometer and gyroscope signals for furthertransmission to external components such as a processor. Such externalor additional sensors may include, but are not limited to, forcesensors, magnetometers, pressure sensors, bend sensors, combinationsthereof, and the like. These external or additional sensors communicatewith the sensor unit by means of an auxiliary communications interface.The digital motion processor can integrate the signal(s) from theseexternal or additional sensors along with the accelerometer andgyroscope signals and perform preprocessing or processing of all of thesignals together, thus further streamlining the data acquisition processand reducing the workload of the external processor (not shown).

In many embodiments, the movement disorder diagnostic device comprises akinetic sensor board (or subject worn external sensor). The kineticsensor board is preferably configured with at least an accelerometer anda gyroscope for quantifying the subject's motion. In some embodiments,the kinetic sensor board comprises at least three gyroscopes and threeorthogonal accelerometers, but in more preferable embodiments the threeof each sensor are replaced by at least one 3-axis accelerometer and atleast one 3-axis gyroscope. The kinetic sensor board also includes amicroprocessor and a power interface section.

In many embodiments, the electrical components of the movement disorderdiagnostic device further include a power receiver. The power receiveris the component which receives the electrical charge from the externalpower source (not shown). The external power source can be any devicefor supplying power to the movement disorder diagnostic device. In someembodiments, the external power source may be a docking station to whichthe movement disorder diagnostic device can be connected, attached,docked, or placed into whereby a physical connection is made between thedocking station and the movement disorder diagnostic device thusallowing power to be transferred via the physical connection. In otherembodiments, the external power source may merely involve plugging themovement disorder diagnostic device into a traditional power outlet. Instill other embodiments, the external power source may be an inductivecharging mat or pad onto which the movement disorder diagnostic deviceis placed and power may be inductively transferred between inductioncoils in the charging mat or pad and the inductive coils in the powerreceiver of the movement disorder diagnostic device, as describedherein. As the power receiver, which may be wireless or wired dependingon the embodiment, receives power, it transfers said power to a powermanager which controls and directs where the incoming power isdelivered. If the movement disorder diagnostic device is not beingpresently used to measure a subject's body movements and is insteadbeing charged, then the power manager directs the incoming power to thedevice's battery for charging. It might be possible, though notnecessarily preferred, for some embodiments to allow charging while theunit is being used to measure a subject's body motions, in which casethe power manager would direct the incoming power to either the batteryor to the micro-controller for powering the device's operation fortesting. However, it is more preferable for the device, during operationfor testing, to be untethered and not in charging mode, and thus thebattery would provide power to the unit for usage and testing purposes.The micro-controller or microprocessor is the internal processing unitthat directs the other components to function. Thus, themicro-controller or microprocessor directs the power manager on where todirect the power it is receiving from either the power receiver or thebattery. An electronic clock operates as commonly known in the art tocontrol synchronization and operation of the device to maximizeefficiency of power usage. The radio of the device controls and carriesout communications between the device components, and between themovement disorder diagnostic device and external devices (not shown).The radio receives power directly from the power manager. As describedherein, the radio may be a Bluetooth® communications device to providewireless communications with external components such as computers orprocessors, data acquisition circuitry, internet or cloud-based memorybanks or databases, and the like, as well as internal components such asthe internal movement disorder diagnostic device memory, microprocessor,and the like. Both internal (between electrical components of thesubject-worn sensor device) and external (between the subject-wornsensor device and external components or devices) communications mayalso be transmitted through wireless, wired, or a combination of bothmethods. The micro-controller comprises algorithms and protocols forcoordinating the operation of at least these internal electricalcomponents, and in some embodiments also for preprocessing or processingsensor data.

The movement disorder diagnostic device of the present invention furtherpreferably comprises a transceiver module, or command module. Preferablythe sensor unit and transceiver/command module are enclosed in the samehousing constituting a single unit, though they may be separate units.The transceiver module includes communications electronics, such as aBluetooth® radio (e.g., BlueGiga WT12) to provide wirelesscommunications with the patient PC, on board memory, a microprocessor(e.g., Silicon Labs C8051F930), and a battery power supply (e.g., KokamLithium Power battery) that supplies power to both the transceivermodule and one or more sensor modules. The transceiver module may alsoinclude a USB port to provide battery recharging and serialcommunications with the patient PC. The transceiver module may alsoinclude a push button input.

In many embodiments, the transceiver/command module contains one or moreelectronic components such as a microprocessor for detecting both thesignals from the gyroscopes and accelerometers. Optionally, the one ormore electronic components also filter the kinetic motion signals, andmore preferably convert these signals, which are in an analog form intoa digital signal for transmission to a remote receiving unit, computeror other similar device. Though, more preferably, the device uses theherein described 3-axis accelerometer and 3-axis gyroscope chip whichcomprises ADC circuitry and thus outputs a digital signal. The one ormore electronic components are attached to the subject as part of themovement disorder diagnostic device. Further preferably, the one or moreelectronic components can receive a signal from the remote receivingunit or other remote transmitters. The one or more electronic componentsmay include circuitry for but are not limited to, for example, electrodeamplifiers, signal filters, analog to digital converter, Bluetooth®radio or other receiver, transmitter or transceiver components, a DCpower source and combinations thereof. The one or more electroniccomponents may comprise one processing chip, multiple chips, singlefunction components or combinations thereof, which can perform all ofthe necessary functions of detecting a kinetic or physiological signalfrom the electrode, storing that data to memory, uploading data to acomputer through a serial link, transmitting a signal corresponding to akinetic or physiological signal to a receiving unit and optionallyreceiving a signal from a remote transmitter. These one or moreelectronic components can be assembled on a printed circuit board or byany other means known to those skilled in the art including but notlimited to an ASIC chip. Preferably, the one or more electroniccomponents can be assembled on a printed circuit board or by other meansso its imprint covers an area less than 4 in², more preferably less than2 in², even more preferably less than 1 in², still even more preferablyless than 0.5 in², and most preferably less than 0.25 in².

Preferably, the circuitry of the one or more electronic components isappropriately modified so as to function with any suitable miniature DCpower source. More preferably, the DC power source is a battery. Themost preferred battery of the present invention is lithium poweredbatteries. Lithium ion batteries offer high specific energy (the numberof given hours for a specific weight), which is preferable.Additionally, these commercially available batteries are readilyavailable and inexpensive. Other types of batteries include but are notlimited to primary and secondary batteries. Primary batteries are notrechargeable since the chemical reaction that produces the electricityis not reversible. Primary batteries include lithium primary batteries(e.g., lithium/thionyl chloride, lithium/manganese dioxide,lithium/carbon monofluoride, lithium/copper oxide, lithium/iodine,lithium/silver vanadium oxide and others), alkaline primary batteries,zinc-carbon, zinc chloride, magnesium/manganese dioxide,alkaline-manganese dioxide, mercuric oxide, silver oxide as well aszinc/air and others. Rechargeable (secondary) batteries includenickel-cadmium, nickel-zinc, nickel-metal hydride, rechargeablezinc/alkaline/manganese dioxide, lithium/polymer, lithium-ion andothers.

In some preferred embodiments, the system is capable of inductivecharging whereby an electromagnetic field is used to transfer energyfrom a charging mat or pad to the device. Preferably in suchembodiments, the charging mat or pad comprises and induction coil thatis used to create an alternating electromagnetic field. When the device,also comprising an induction coil, is placed on the charging mat or pad,the devices induction coil draws power from the electromagnetic fieldcreated by the charging mat's or pad's induction coil. The device's thenconverts this drawn power from electromagnetic field energy intoelectrical current and uses this electrical current to charge thedevice's battery.

Optionally, the data acquisition circuitry is designed with the goal ofreducing size, lowering (or filtering) the noise, increasing the DCoffset rejection and reducing the system's offset voltages. The dataacquisition circuitry may be constrained by the requirements forextremely high input impedance, very low noise and rejection of verylarge DC offset and common-mode voltages, while measuring a very smallsignal of interest. Additional constraints arise from the need for a“brick-wall” style input protection against ESD and EMI. The exactparameters of the design, such as input impedance, gain and passband,can be adjusted at the time of manufacture to suit a specificapplication via a table of component values to achieve a specificfull-scale range and passband.

Also optionally, a low-noise, lower power instrumentation amplifier isused. The inputs for this circuitry is guarded with preferably, externalESD/EMI protection, and very high-impedance passive filters to reject DCcommon-mode and normal-mode voltages. Still more preferably, theinstrumentation amplifier gain can be adjusted from unity toapproximately 100 to suit the requirements of a specific application. Ifadditional gain is required, it preferably is provided in a second-orderanti-bias filter, whose cutoff frequency can be adjusted to suit aspecific application, with due regard to the sampling rate. Still yetmore preferably, the reference input of the instrumentation amplifier istightly controlled by a DC cancellation integrator servo that usesclosed-loop control to cancel all DC offsets in the components in theanalog signal chain to within a few analog-to digital converter (ADC)counts of perfection, to ensure long term stability of the zeroreference.

Further optionally, where analog signals are acquired, such signals areconverted to a digital form. This can be achieved with an electroniccomponent or processing chip through the use of an ADC. More preferably,the ADC restricts resolution to 16-bits due to the ambient noiseenvironment in such chips. Despite this constraint, the ADC remains thepreferable method of choice for size-constrained applications such aswith the present invention unless a custom data acquisition chip is usedbecause the integration reduces the total chip count and significantlyreduces the number of interconnects required on the printed circuitboard.

Preferably, the circuitry of the sensor board comprises a digitalsection. More preferably, the heart of the digital section of the sensorboard is a micro-controller or processor. The microcontroller orprocessor preferably contains sufficient data and program memory, aswell as peripherals which allow the entire digital section to be neatlybundled into a single carefully programmed processing chip. Still morepreferably, the onboard counter/timer sections are used to produce thedata acquisition timer.

Preferably, the circuitry for the one or more electronic components isdesigned to provide for communication with external quality control testequipment prior to sale, and more preferably with automated final testequipment. In order to supply such capability without impacting thefinal size of the finished unit, one embodiment is to design acommunications interface on a separate printed circuit board (PCB) usingthe SPI bus with an external UART and level-conversion circuitry toimplement a standard serial interface for connection to a personalcomputer or some other form of test equipment. The physical connectionto such a device requires significant PCB area, so preferably thephysical connection is designed to keep the PCB at minimal imprint area.Optionally, the physical connection is designed with a break-off tabwith fingers that mate with an edge connector. This allows all requiredfinal testing and calibration, including the programming of theprocessing chip memory, can be carried out through this connector, withtest signals being applied to the analog inputs through the normalconnections which remain accessible in the final unit. By using edgefingers on the production unit, and an edge connector in the productiontesting and calibration adapter, the system can be tested and calibratedwithout leaving any unnecessary electronic components or too large a PCBimprint area on the final unit. More preferably, no break-off tabs arerequired where a pogo-pin test pad design is used allowing the PCB to betested without breaking apart.

Preferably, the circuitry for the one or more electronic componentscomprises nonvolatile, rewriteable memory for storing kinematic data, aswell as RAM used to store operational data such as the pending mode(i.e., sleep or test mode), period and number of seconds to record data,daily alarm time, amount of time to collect data, and the like.Preferably, enough nonvolatile memory is included to record at least 8hours of kinematic data, though preferably more. Alternatively, if thecircuitry for the one or more electronic components doesn't comprisenonvolatile, rewriteable memory then an approach should be used to allowfor reprogramming of the final parameters such as radio channelizationand data acquisition and scaling. Without nonvolatile, rewriteablememory, the program memory can be programmed only once. Therefore oneembodiment of the present invention involves selective programming of aspecific area of the program memory without programming the entirememory in one operation. Preferably, this is accomplished by settingaside a specific area of program memory large enough to store severalcopies of the required parameters. Procedurally, this is accomplished byinitially programming the circuitry for the one or more electroniccomponents with default parameters appropriate for the testing andcalibration. When the final parameters have been determined, the nextarea is programmed with these parameters. If the final testing andcalibration reveals problems, or some other need arises to change thevalues, additional variations of the parameters may be programmed. Thefirmware of various embodiments of the present invention scans for thefirst blank configuration block and then uses the value from thepreceding block as the operational parameters. This arrangement allowsfor reprogramming of the parameters up to several dozen times, with nosize penalty for external EEPROM or other nonvolatile RAM. The circuitryfor the one or more electronic components has provisions for in-circuitprogramming and verification of the program memory, and this issupported by the breakoff test connector, as well as the pop-pin testpad. The operational parameters can thus be changed up until the time atwhich the test connector is broken off just before shipping the finalunit. Thus the manufacturability and size of the circuitry for the oneor more electronic components is optimized. Most preferably, however,the system is designed to allow for over-the-air programming even oncethe circuit design has been completed and the circuit has been installedinto the movement disorder diagnostic device. In such embodiments, thefirmware contains a boot-loading program that, once turned on, looks forprogramming signals. Thus, such programming signals can be delivered andthe device updated, even after manufacture and shipment to a clinic, oreven when in the possession of a subject.

Preferably the circuitry of the one or more electronic componentsincludes an RF transmitter and/or an RF receiver, or a RF transceiver.Still more preferably the circuitry of the one or more electroniccomponents includes a Bluetooth® radio system requiring an average ofabout 42 mA of electrical current to operate. Another feature of thecircuitry of the one or more electronic components preferably is anantenna. The antenna, preferably, is integrated in the rest of thecircuitry. The antenna can be configured in a number of ways, forexample as a single loop, dipole, dipole with termination impedance,logarithmic-periodic, dielectric, strip conduction or reflector antenna.The antenna is designed to include but not be limited to the bestcombination of usable range, production efficiency and end-systemusability. Preferably, the antenna consists of one or more conductivewires or strips, which are arranged in a pattern to maximize surfacearea. The large surface area will allow for lower transmission outputsfor the data transmission. The large surface area will also be helpfulin receiving high frequency energy from an external power source forstorage. Optionally, the radio transmissions of the present inventionmay use frequency-selective antennas for separating the transmission andreceiving bands, if a RF transmitter and receiver are used on theelectrode patch, and polarization-sensitive antennas in connection withdirectional transmission. Polarization-sensitive antennas consist of,for example, thin metal strips arranged in parallel on an insulatingcarrier material. Such a structure is insensitive to or permeable toelectromagnetic waves with vertical polarization; waves with parallelpolarization are reflected or absorbed depending on the design. It ispossible to obtain in this way, for example good cross polarizationdecoupling in connection with linear polarization. It is furtherpossible to integrate the antenna into the frame of a processing chip orinto one or more of the other electronic components, whereby the antennais preferably realized by means of thin film technology. The antenna canserve to just transfer data or for both transferring data to and forreceiving control data received from a computer device and/or receivingunit which can include but is not limited to a wireless relay, acomputer or a processor system. Optionally, the antenna can also serveto receive high-frequency energy (for energy supply or supplement). Inany scenario, only one antenna is required for transmitting data,receiving data and optionally receiving energy. Optionally, directionalcouples can be arranged on the transmitter outputs of the electrodepatch and/or the computer device and/or receiving unit. The couplersbeing used to measure the radiated or reflected radio wave transmissionoutput. Any damage to the antenna (or also any faulty adaptation) thuscan be registered, because it is expressed by increased reflectionvalues.

An additional feature of the present invention is an optionalidentification unit. By allocating identification codes—a patient code,the computer device and/or receiving unit is capable of receiving andtransmitting data to several subjects, and for evaluating the data ifthe computer device and/or receiving unit is capable of doing so. Thisis realized in a way such that the identification unit has controllogic, as well as a memory for storing the identification codes. Theidentification unit is preferably programmed by radio transmission ofthe control characters and of the respective identification code fromthe programming unit of the computer device and/or receiving unit to thepatient worn unit. More preferably, the unit comprises switches asprogramming lockouts, particularly for preventing unintentionalreprogramming.

In any RF link, errors are an unfortunate and unavoidable problem.Analog systems can often tolerate a certain level of error. Digitalsystems, however, while being inherently much more resistant to errors,also suffer a much greater impact when errors occur. Thus the presentinvention, when used as a digital system, preferably includes errorcontrol sub architecture. Preferably, the RF link of the presentinvention is digital. RF links can be one-way or two-way. One-way linksare used to just transmit data. Two-way links are used for both sendingand receiving data.

If the RF link is one-way error control, then this is preferablyaccomplished at two distinct levels, above and beyond the effort toestablish a reliable radio link to minimize errors from the beginning.At the first level, there is the redundancy in the transmitted data.This redundancy is performed by adding extra data that can be used atthe computer device and/or receiving unit or at some station to detectand correct any errors that occurred during transit across the airwaves.This mechanism known as Forward Error Correction (FEC) because theerrors are corrected actively as the signal continues forward throughthe chain, rather than by going back to the transmitter and asking forretransmission. FEC systems include but are not limited to Hamming Code,Reed-Solomon and Golay codes. Preferably, a Hamming Code scheme is used.While the Hamming Code scheme is sometimes maligned as being outdatedand underpowered, the implementation in certain embodiments of thepresent invention provides considerable robustness and extremely lowcomputation and power burden for the error correction mechanism. FECalone is sufficient to ensure that the vast majority of the data istransferred correctly across the radio link. Certain parts of the packetmust be received correctly for the receiver to even begin accepting thepacket, and the error correction mechanism in the computer device and/orreceiving unit reports various signal quality parameters including thenumber of bit errors which are being corrected, so suspicious datapackets can be readily identified and removed from the data stream.

Preferably, at a second, optional level, an additional line of defenseis provided by residual error detection through the use of a cyclicredundancy check (CRC). The algorithm for this error detection issimilar to that used for many years in disk drives, tape drives, andeven deep-space communications, and is implemented by highly optimizedfirmware within the electrode patch processing circuitry. Duringtransmission, the CRC is first applied to a data packet, and then theFEC data is added covering the data packet and CRC as well. Duringreception, the FEC data is first used to apply corrections to the dataand/or CRC as needed, and the CRC is checked against the message. If noerrors occurred, or the FEC mechanism was able to properly correct sucherrors as did occur, the CRC will check correctly against the messageand the data will be accepted. If the data contains residual errors(which can only occur if the FEC mechanism was overwhelmed by the numberof errors), the CRC will not match the packet and the data will berejected. Because the radio link in this implementation is strictlyone-way, rejected data is simply lost and there is no possibility ofretransmission.

More preferably, the RF link utilizes a two-way (bi-directional) datatransmission. By using a two-way data transmission the data safety issignificantly increased. By transmitting redundant information in thedata emitted by the electrodes, the computer device and/or receivingunit is capable of recognizing errors and request a renewed transmissionof the data. In the presence of excessive transmission problems such as,for example transmission over excessively great distances, or due toobstacles absorbing the signals, the computer device and/or receivingunit is capable of controlling the data transmission, or to manipulateon its own the data. With control of data transmission it is alsopossible to control or re-set the parameters of the system, e.g.,changing the transmission channel. This would be applicable for exampleif the signal transmitted is superimposed by other sources ofinterference then by changing the channel the computer device and/orreceiving unit could secure a flawless and interference freetransmission. Another example would be if the signal transmitted is tooweak, the computer device and/or receiving unit can transmit a commandto increase its transmitting power. Still another example would be thecomputer device and/or receiving unit to change the data format for thetransmission, e.g., in order to increase the redundant information inthe data flow. Increased redundancy allows transmission errors to bedetected and corrected more easily. In this way, safe data transmissionsare possible even with the poorest transmission qualities. Thistechnique opens in a simple way the possibility of reducing thetransmission power requirements. This also reduces the energyrequirements, thereby providing longer battery life. Another advantageof a two-way, bi-directional digital data transmission lays in thepossibility of transmitting test codes in order to filter out externalinterferences such as, for example, refraction or scatter from thetransmission current. In this way, it is possible to reconstruct falselytransmitted data.

The computer device and/or receiving unit of various embodiments of thepresent invention can be any device known to receive RF transmissionsused by those skilled in the art to receive transmissions of data. Thecomputer device and/or receiving unit, by way of example but notlimitation, can include a communications device for relaying thetransmission, a communications device for re-processing thetransmission, a communications device for re-processing the transmissionthen relaying it to another computer device and/or receiving unit, acomputer with wireless capabilities, a PDA with wireless capabilities, aprocessor, a processor with display capabilities, a desktop computer,laptop computer, tablet computer, smart phone, and combinations of theseor like devices. Optionally, the computer device and/or receiving unitcan further transmit data both to another device and/or back. Furtheroptionally, two different computer devices and/or receiving units can beused, one for receiving transmitted data and another for sending data.For example, with the movement disorder diagnostic system of the presentinvention, the computer device and/or receiving unit of the presentinvention can be a wireless router, which establishes a broadbandInternet connection and transmits the physiological signal to a remoteInternet site for analysis, preferably by the subject's physician.Another example is where the computer device and/or receiving unit is aPDA, computer, tablet or cell phone, which receives the physiologicaldata transmission, optionally re-processes the information, andre-transmits the information via cell towers, land phone lines or cableto a remote site for analysis. Another example is where the computerdevice and/or receiving unit is a computer or processor, which receivesthe data transmission and displays the data or records it on somerecording medium, which can be displayed or transferred for analysis ata later time.

The digitized kinetic or physiological signal is then transmittedwirelessly to a computer device and/or receiving unit. This computerdevice and/or receiving unit allows the subject wide movement.Preferably, the computer device and/or receiving unit can pick up andtransmit signals from distances of greater than about 5 feet from thesubject, more preferably greater than about 10 feet from the subject,even more preferably greater than about 20 feet from the subject, stilleven more preferably greater than about 50 feet from the subject, stilleven more preferably greater than about 200 feet from the subject, andmost preferably greater than about 500 feet from the subject. Thecomputer device and/or receiving unit is used to re-transmit the signalbased in part from the movement or physiological signal from themovement disorder diagnostic device wirelessly or via the internet toanother monitor, computer or processor system. This allows the clinicianor monitoring service to review the subject's movement or physiologicalsignals and if necessary to make a determination, which could includemodifying the patients treatment protocols.

Optionally, the system of the present invention includes some form ofinstruction, which can be in written form on paper or on a computermonitor, or on a video. Optionally, a video is used which instructs thesubjects to perform a series of tasks during which their kinetic motionand/or EMG and/or other physiological signals related to their motioncan be measured. Since the system of the present invention is preferablyused in the subject's home, a video giving directions and/or describingvarious tasks to be performed by the subject is included with thesystem. The video may be accessed or viewed for example but not by wayof limitation through use of video tape, DVD, podcast as part ofcomputer software provided, through the internet, or the like. Thedirections could include but are not limited to instructions on how todon the device, how to turn the device on, and the like. The descriptionof various tasks could include but is not limited to exercises which aretypically used by a technician, clinician or physician to evaluate asubject with a movement disorder including but not limited to handgrasps, finger tapping exercises, other movements and the like. Oneembodiment of a video includes the technician, clinician or physicianlooking into the camera, as they would a patient, and instructing themon device setup, instructing the patients through each of the tasks tobe performed, providing verbal encouragement via video after a task, andasking subject's to repeat a task if it was not completed. Preferably,these video clips are edited and converted to MPEG or other similar filetypes either automatically or using editing software. For movementdisorders such as Parkinson's disease preferably the technician,clinician or physician instructs the user through multiple tasks as perthe UPDRS, TRS, or similar scale guidelines including but not limited torest tremor, postural tremor, action tremor, all bradykinesia tasks(including but not limited to finger taps, hand grasps, andpronation/supination tasks), and/or rigidity tasks. More preferably, ifthe video is linked to the user interface software, the software willautomatically detect if a subject has performed the requested task andprovide feedback through the video to either repeat the task or continueto the next task. Still more preferably, once the user has setup thedevice, it will continually record the subject's movement data(including before and after any directed video tasks), be able toquantify the severity of the subject's symptoms during activities ofdaily living, and communicate that information with the clinician andsubject through interface software, video, or the like.

The present invention includes various methods of measuring and scoringthe severity of a subject's movement disorder. These methods include anumber of steps which may include but are not limited to measuring asubject's external body motion; transmitting wirelessly a signal basedin part on the subject's measured external body motion; receiving thewirelessly transmitted signal; downloading data from memory; and scoringthe severity of a subject's movement disorder based in part on thewirelessly transmitted or downloaded signal. Optionally, anelectromyogram of the subject's muscle activity and/or otherphysiological signals may be obtained and used in part to score theseverity of the subject's movement disorder.

Several preferred embodiments of the present invention include a trainedscoring algorithm to determine and provide objective scoring frommovement data acquired by the movement disorder diagnostic device. Thetrained scoring algorithm in part comprises a mathematical model orquantitative representation, used to process kinematic features computedfrom the movement data and may include some of those steps known tothose skilled in the art. In some embodiments of the present invention,the scoring may done on a continuously variable scale of 0-4 with scoressubstantially similar to or predictive of scores that would be given onthe Unified Parkinson's Disease Ratings Scale by an expert clinician.(“Expert clinician” for the purposes of this application is taken tomean a doctor, nurse, researcher, or other medical or scientificprofessional trained for and sufficiently experienced in the task ofinterest, e.g., motor function assessment using the UPDRS, or DBSprogramming.)

The present invention also preferably includes DBS parameter controlmethods and tuning algorithms for determining and setting the DBSparameters used to deliver DBS therapy to the subject. In manyembodiments, the parameter control methods and algorithms utilize asystem of tuning maps, or other parameter display or visualizationmethods or tools, for DBS programming. Although the term ‘tuning map’ isused throughout this application, it is intended that tuning mapsinclude any such method or tools that may be used for displaying therapyparameters or settings for human review and/or analysis. As notedherein, in the present invention, the tuning maps are preferably onlyutilized for optional clinician, physician or technician review of thesecond levels or optimized levels of therapy parameters or settings. Thetuning maps utilized by the present invention are a tool used forrecording DBS parameters, the subject's response to stimulation at thoseparameters, and allowing a clinician, physician or technician tooptionally or periodically review parameters and settings. Preferably,when utilized, the tuning map is a two-dimensional representation of athree-dimensional graph or display of data.

The subject is first screened and determined to be a viable candidatefor DBS therapy, and then has at least one DBS lead surgically implantedinto his or her brain. The screening process preferably involvesproviding the subject with a diagnostic device for monitoring andassessing the subject's movement disorder systems. Generally, a DBStherapy system will include one or more implanted leads with each leadhaving one or more electrodes. These leads are connected to a pulsegenerator, which generally is also implanted with the leads. The pulsegenerator can be implanted in the cranium or in some cases wiring fromthe leads will be threaded down the subject's neck and the pulsegenerator will be implanted or embedded in the subject's upper chest.The pulse generator will run on a battery, which can in some casesrecharged through techniques such as inductive coupling. The DBS therapysystem can be adjusted generally through communication between aprogramming module or unit and the impulse generator. Such a system, asan example, is described in U.S. patent application Ser. No. 12/818,819,filed on Jun. 18, 2010, which is hereby incorporated by reference. Othersystems as known or later developed in the art can also be adjusted withthe devices, method and systems of the present invention. Thus, becauseof the highly invasive nature of therapies such as DBS, requiringsurgical implantation of the therapy device, the present inventionprovides the screening capabilities to ensure the subject would benefitfrom such a therapy before undergoing the costly and onerous surgicalprocedure.

The subject may utilize this device at home and during other normal lifeactivities as well, or in a clinical setting, and during the performanceof motor and cognitive tests, and while taking his or her prescribedmedications for treatment and management of the movement disordersymptoms. The device monitors and records the occurrence of thesesymptoms and then analyzes the data by means of algorithm(s) designed toaccount for the multitude of variables including demographic information(age, gender, weight, blood pressure, physical activity, medication use,disease duration, Hoehn & Yahr, marital status/caregiver support,patient expectations, and the like), the type of anticipated DBS therapy(DBS target, unilateral/bilateral implant, constant current versusconstant voltage, and the like), non-motor response (UPDRS parts I andII scores, cognition and quality of life assessments, neuropsychologytests, and the like), motor response (UPDRS parts III and IV scores),sensor recordings of symptom occurrence and severity, response tomedication, and the like. Generally, subjects who respond favorably totypical medications tend to respond well to DBS therapy. The algorithmanalyzes all of the data and makes a determination as to whether thepatient is likely to be a good candidate for DBS therapy. The algorithmmay optionally employ any one, or a combination of, statistical modelscurrently known to those in the art, including, but not limited tolinear and non-linear classification methods such as logisticregression, artificial neural networks, k-means clustering, and thelike. The algorithm may output the determination in different ways. Insome embodiments, the algorithm may provide a binary output indicatingthat the subject is or is not a good candidate for DBS, in other words areport or display that indicates a Go/No go result on whether thesubject would or would not benefit from such therapy. In otherembodiments, the algorithm may provide a percent likelihood of favorableDBS outcomes for the subject. Still other embodiments may present themultitude of data described above in a chart or graph format in order toallow a clinician, physician or technician to review the data andresults and confirm or deny that the subject would benefit from suchtherapy. By way of non-limiting example, various embodiment may employ avisual display that depicts a pie chart wherein the pie chart ispopulated showing the measured and quantified occurrences of asymptom(s) such as tremor throughout the day. Any other method known tothose skilled in the art for displaying the test results and optionallythe input data, or combinations of both, can be envisioned forpresenting the data to a clinician, physician or technician for optionalreview of the screening viability determination. Additionally, thealgorithm may provide suggested DBS lead placements in the subject'sbrain based at least in part on the symptoms and side effects thesubject experiences, their severity, and the like. If the subject isdetermined to be a favorable candidate, the clinician then initiates theprocess for DBS therapy, which begins with the surgical implantation ofat least one DBS lead into the subject's brain. The main purpose of thescreening process is to provide a pre-surgical indication of whether thesubject would benefit from DBS therapy. This minimizes the likelihood ofneedless surgery and risk for the subject, as well as time, cost, andresources utilized.

For initial DBS tuning, it may be preferable to perform a monopolarreview, which is using a single DBS contact in the monopolarconfiguration. However, bipolar, or greater, review may be accomplishedas well with the present invention. A single DBS lead has severalcontact points, or electrodes, which can be used to administer theelectrical stimulation. Typically, a DBS lead has at least one groundcontact, and at least 3 battery contacts for delivering the electricalstimulation, though fewer or more battery contacts may be included. Oncethe lead, or leads, is implanted into the subject's brain, the subjectthen undergoes an initial programming session. During the initialprogramming session, a clinician enters a set of initial test variables(as described above), and administers the electrical impulse to thesubject's brain. Typically, the initial test parameters are set andfixed, and then in later iterations the amplitude (voltage or current),as well as other variables are gradually increased or otherwise changed.The results of the impulse may be recorded in a tuning map for optionalreview indicating the effect which the given set of parameters had onthe subject's symptoms, feelings, and the like, and are simultaneouslycommunicated to the tuning algorithm(s). The subject is generally awakefor the programming sessions and gives feedback to the clinicianregarding any sensations or effects that the subject experiences. Theresults may include any sort of measured, observed, or calculatedresponse, or combinations thereof including, but not limited to, sensorrecordings (for quantifying symptoms as described above), patientresponses and perceptions, clinician observations, and clinician scores(e.g., UPDRS, MDS-UPDRS, and the like). In some embodiments, it ispossible that the tuning process may be entirely automated such that thetuning map is populated entirely by, and/or the algorithm(s) is suppliedwith sensor recordings and/or measured and quantified motor symptom dataof the subject's response to the DBS therapy and no human observation orcalculation is required. Based on the results of the initial testparameters, the tuning map is populated, and the tuning algorithm(s)changes the parameters to more effectively address the subject'ssymptoms, and the process is repeated. Preferably, in such embodiments,the tuning map is populated simultaneously with supplying themeasurements to the algorithm(s), and the tuning map remains a hidden ordormant feature that can optionally be accessed for review of theparameters and settings. Typically, the end result of the tuning processis to optimize the effectiveness of the therapy (i.e., decrease theseverity and occurrence of symptoms as much as possible) whileminimizing the volume of activated brain tissue, but the particulargoals and needs of the subject will dictate exactly what the desiredresult is for each subject.

Many embodiments of the present invention employ an intelligent systemprogramming capability that greatly decreases the amount of clinician“guess-work” involved in selecting the iterations of DBS parametervalues by providing an expert system that efficiently determinesappropriate DBS settings. Similar to above, for the first postoperativeprogramming session, the system performs an automated monopolar survey.The subject may wear a motion sensor unit comprising sensors formeasuring movement, and performs motor assessments at various DBSsettings. Stimulation is incrementally increased from zero at eachcontact until symptoms stop improving as measured by the motion sensorunit, perceptions, clinician observations or scores, or the like, oruntil side effects appear as measured by the motion sensor unit, theclinician, or the patient. In many embodiments, adjustments will bebased on current rather than voltage since it is the amount of currentdelivered to a specific target that determines the functional response.For constant current IPGs, the current amplitude will be set directlyand for constant voltage IPGs, the voltage amplitude will be set basedon the required current and impedance measured on the electrode.Preferably, the system is capable of operating in either constantcurrent or constant voltage modes, depending on the clinician'spreference and the needs of the particular subject. The monopolar surveyhelps determine the functional anatomy around the DBS lead site andnarrows the search space for determining an optimal set of programmingparameters. A therapeutic window will be defined as the region in whicha patient exhibits optimal symptomatic benefits without side effects.This therapeutic window will be valuable at the initial postoperativeprogramming session as well as all future adjustment sessions fordetermining the current amplitude when side effects begin to occur oneach contact. This therapeutic window is then used to define a sideeffect region. The system includes internal electric field modeling todetermine how this side effect region can be avoided, possibly byshaping the electric field with a bi- or tripolar configuration oraltering the pulse width. Bipolar or tripolar configuration refers tothe simultaneous delivery of electrical impulses from two or three,respectively, contacts on the DBS lead to shape the electrical fielddelivered to the subject's brain. For monopolar stimulation, currentfalls off proportionally to the distance from the negative electrodecontact. For bipolar stimulation, current decreases proportional to thesquare of the distance to the negative contact, but increases by thesquare of the distance between the negative and positive contacts.Efficient stimulation algorithms are used to find a set of parametersthat optimize for efficacy while minimizing side effects and batteryusage. The patient and/or clinician will be able to give higher weightto a given item, parameter, or symptom (e.g., tremor severity) that maybe most important to him or her. Many clinicians are ignorant of thebattery voltage of the IPG battery and therefore unaware that a slightincrease of the stimulation amplitude above the battery voltage willactivate voltage doubler or tripler circuits in the IPG, significantlyincreasing battery drain and shortening battery life by half. Thealgorithms will automatically avoid increasing voltage above the batteryvoltage unless necessary for finding a therapeutic window. After theautomated monopolar survey is completed and a patient-specificfunctional map is developed during the initial postoperative programmingvisit, subsequent programming adjustments will be much simpler andfaster.

Basing the algorithm(s) on functional, rather than structural, anatomyhas several advantages. First, most DBS programmers are not imagingexperts and may not have the wherewithal to correctly interpret complexanatomies. More importantly, the therapeutic mechanisms of DBS arelargely unknown. The optimal stimulation location differs acrosspatients and is based on functional rather than structural anatomy.Therefore, the system will be individualized to each subject's responseand be far superior to recently developed DBS programming aids, whichrely on anatomical assumptions, imaging, and statistical modeling toestimate the electric field at various anatomical targets.

The intelligent system programming capability takes the results of theinitial test parameters and automatically populates the tuning map whilesimultaneously providing these results to an algorithm(s). The system'stuning algorithm(s) analyze these results and provide the next iterationof DBS parameters. These provided parameters or settings may be reviewedand possibly edited by the clinician, physician or technician, or may beautomatically entered into the subject's therapy device thus programmingthe therapy device to operate according to those settings. Effectively,the system provides optimized DBS parameters or settings which eitherare automatically implemented, or may act as a guide for the clinicianin setting the IPG for the next iteration of testing (particularly forthe initial programming session). This reduces the clinician's need toperform the analysis and determine which parameters to change and howmuch to change them. The clinician may have the option to edit or electany one or combination of the system's suggested parameters for the nextiteration. This intelligent programming system may be performedin-clinic during a traditional programming appointment, whereby thesystem provides the suggested DBS parameters or settings to theclinician and the clinician can review and edit the parameters orsettings through the software which in turn adjusts the settings andparameters on the IPG. Alternatively, the intelligent programming maytake place remotely whereby the system automatically and intelligentlyprovides optimized parameters or settings and programs them into thesubject's therapy device, or communicates any data and suggested DBSparameter settings to the clinician, physician or technician who islocated some distance away while the subject remains at home, and theclinician then reviews and elects to approve or edit the suggestedsettings, which are sent to the IPG to update the parameters of the DBSadministered to the subject, or still further the clinician may instructthe diagnostic device to perform another iteration of testing, ratherthan editing the suggested parameters or settings herself. Where theclinician, physician or technician does perform the option or periodicreview, the data (e.g., parameters and settings, test results, and thelike) may be displayed for his or her review in a tuning map asdescribed. Because the clinician is not required to be physicallypresent at the time of programming, the system instead may rely onsystem and user reports, which are sent to the clinician. These reportsmay be made by the system sending reports to the clinician, video and/oraudio conferences between the subject and the clinician, the subjectkeeping a medication diary to report medication schedules and symptomoccurrence and severity, transmitted tuning maps, and the like.

Some embodiments of the present invention provide the clinician,physician or technician the ability to manually make the determinationas to what therapy parameters to use with the subject's therapy devicebased in part on the tuning map or data corresponding to the subject'smeasured and quantified motor symptoms or based on other data measuredby the movement disorder diagnostic device from the subject. Again, thisis solely an optional review designed for periodic analysis of thealgorithm(s)' function and to ensure that the subject's needs are beingmet adequately and safely. The present invention further optionallyallows the clinician, physician or technician the ability to reviewrecommended second level therapy parameters before or after thosetherapy parameters or settings are entered into the therapy device andto change those recommended settings.

Additionally, other embodiments of the present invention may includeintelligent remote programming methods and algorithms utilizing adatabase, which may be cloud-based in some embodiments, allowing forremote DBS adjustments being possible without the subject even leavinghis or her home, and without clinician involvement. The system mayprovide automated, objective scoring and tuning algorithms to take theprogramming expertise out of the hands of a clinician, and enablehigh-quality programming to all DBS recipients, regardless of proximityto or availability of expert programmers. Ideally, the subject would nothave to travel to the clinic or facility for programming unless aproblem was detected requiring personal medical care. Such embodimentsnecessarily include the integrated system programming capability wherebythe software directly communicates with the hardware to set the DBSparameters according to the values entered into the software in order toenable the periodic or optional review by the clinician, physician ortechnician. For such optional or periodic review, rather than in-clinicprogramming sessions, the software would communicate with the DBShardware, which is located remotely, implanted into the subject. Inthese embodiments, the implanted device would perform the intelligentsystem analysis as above, creating a suggested set of DBS parameters forthe particular subject, and then securely communicates all the data andsuggested parameters to a centralized or cloud-based database, whichanalyzes all the information and then sends programming commands to thesubject's IPG to change the DBS settings. This database and intelligentremote system allow for continued or repeated DBS tuning withoutrequiring the patient to travel to a clinician, and without requiring aclinician to spend the time analyzing subject data. The benefits of sucha system go beyond the convenience of minimizing travel time and accessto clinicians and include the ability to deliver such reports atvirtually any time (the subject and clinician are not tied to aparticular appointment time and window, and the clinician can review anydata at any time if desired), continuous and repeated monitoring of thesubject and system's status, and delayed monitoring whereby results ofchanged parameters can be monitored later, which is particularly usefulfor symptoms that may not react to changes rapidly (i.e., during thenormal clinical appointment time period).

Further, the system preferably includes the capability to performhardware diagnostic tests remotely of any and all of the individualunits or modules used with the present invention, including thesubject's therapy device (e.g., implanted pulse generator), movementdisorder diagnostic device, programmer unit, and the like. The hardwarein such embodiments is able to monitor and/or periodically interrogatethe system to detect changes in system conditions such as batterystatus, electrode impedance, and the like. The system then sends theresults of these diagnostic tests back to the clinician who can monitorthem to determine if a problem arises requiring the subject to return tothe clinic for adjustments, repairs, or other such purposes. Furtherstill, such embodiments using remote programming and control may includemedication delivery systems as well. Such delivery systems include adrug reservoir for holding and storing medication, and infusion pump fordelivering said medication from the reservoir to the subject. Suchembodiments may determine based on recorded signals that the subject'ssymptoms are particularly severe or occurring more frequently.

Some embodiments may optionally include a closed-loop or semi-closedloop drug titration system. In such embodiments, when the subject'sprescribed medication is initially taken or delivered, the system thenmonitors the subject's symptoms. The system continues to monitor thesymptoms until and after it detects that the subject's symptomsincrease, maintain, or only very slightly decrease in severity and rateof occurrence. In a semi-closed loop system, a report, warning, alert,or some other signal would then be sent to the subject or to thesubject's clinician. In such case, the subject could take moremedication, or the clinician could send a command for an integrated drugdelivery pump to administer another dose. In a close-loop system, upondetection of the above indicators, the system would automaticallyadminister an additional dose of medication through an integratedmedication delivery pump. In either case, the system is capable ofsubstantially continuous symptom monitoring to determine when thesubject is experiencing an increase in symptom activity, ineffectivemedication delivery, or a wearing off of medication in order toadminister additional medication to control the subject's symptoms.Further, such embodiments must also be able to monitor and detect theoccurrence of side effects arising from the medication, and to stopadministering medication when such side effects begin to manifest.

The above systems, devices, and methods are further contemplated for usein treating various mental health disorders, particularly majordepression, bipolar disorder, and obsessive compulsive disorder. Inparticular treatment of mental health disorders would benefit from thepatient screening system and method for determining if the patient wouldbenefit from DBS therapy in dealing with his or her disorder, as well asthe integrated and intelligent programming systems and methods for bothin-clinic and remote programming of the DBS device once implanted.

The Applicants herein incorporate the following U.S. Pat. ApplicationNos. by reference: Ser. No. 11/082,668 filed Mar. 17, 2005, and Ser. No.11/432,583 filed May 11, 2006.

FIG. 1 illustrates the therapeutic device programming (or “tuning,” or“parameter settings adjustment”) process with one embodiment of theinvention. A subject 1 has a therapy device (not shown), which in theillustrated case is a therapy device for the treatment of a movementdisorder, such as an implanted DBS device. Subject 1 wears a movementdisorder diagnostic device comprising a sensor unit 2 and a commandmodule 3. The sensor unit 2 comprises at least one sensor(s), preferablya physiological or movement sensor(s), such as accelerometers and/orgyroscopes (both not shown), or other similar sensors, as well as atransmission system (not shown). In one preferred embodiment, the sensorunit 2 comprises three orthogonal accelerometers and three orthogonalgyroscopes, or more preferably at least one 3-axis accelerometer and atleast one 3-axis gyroscope. Preferably, where the at least one sensor isan accelerometer and/or a gyroscope, these aremicro-electrical-mechanical (MEMS) accelerometers or gyroscopes. In apreferred embodiment, a single chip containing both a 3-axisaccelerometer and a 3-axis gyroscope is used, rather than using separatesensors. An example of such a combined sensor chip is the InvensenseMPU-6000. The transmission system may be wired or wireless, and maycommunicate via any medium and any transmission protocol known to thoseskilled in the art. In the illustrated embodiment, the sensor unit 2communicates sensor readings to a command module 3 over a small flexibletransmission cable 4, though this transmission could also be conductedwirelessly. In the more preferred embodiment where both the sensor unit2 and command module 3 are combined in a single housing constituting theentire movement disorder diagnostic device, the two modules may beintegrated into the same electronics thus eliminating the need for wiredor wireless communication between separate modules. In the illustratedembodiment, the sensor unit 2 is worn on the middle phalange of themiddle finger and the command module 3 is worn on the wrist using awristband, though the placement of the sensor unit 2 and command module3 may vary depending upon the symptoms of the movement disorder.Alternate placements could include other fingers, the ankle, foot,shoulder, or elsewhere on the trunk of the body or on any part of anyextremity. While the illustrated embodiment shows the sensor unit 2 andthe command module 3 as having separate enclosures, permitting for alighter-weight sensor unit 2 that is easily worn on the finger, inalternate embodiments the sensor unit 2 and command module 3 may beintegrated into a single enclosure. In such embodiments where the sensorunit and command module are combined into a single enclosure forming themovement disorder diagnostic device, all components of each unit areenclosed or attached to the single enclosure, including, but not limitedto the units and modules themselves, any power supply and communicationelectronics required for operation.

The command module 3 may provide numerous functions including, but notlimited to supplying power to the sensor unit 2, storing data in memory,transmitting data. Preferably, it is controlled by firmware inprocessor, for example an Analog Devices ADuC7020 processor. The dataacquisition (DAQ) section samples finger sensor unit data at 128 Hz foreach of the six channels. Optional onboard memory preferably provides atleast 12 hours of data storage. Some embodiments do not contain internalstorage, but rather transmit the data substantially in real-time to areceiver unit 5, a centralized database (not shown) or to a cloud-baseddatabase (not shown). Still other embodiments utilize onboard, temporarydata storage as well as substantially real-time data transmission to areceiver unit 5, centralized database (not shown) or a cloud-baseddatabase (not shown). A lithium-based battery provides at least 12 hoursof continuous use and is rechargeable by a computer through a LEMO, orsimilar connector, to USB connector cable. The command module 3 alsointegrates a membrane switch label (not shown) with LED indicators forpower and charging (not shown). Three membrane switches inside the label(not shown) provide on/off control and two subject diary inputs. Thecommand module 3 may perform rudimentary signal processing, such asfiltering and analog-to-digital conversion, on the movement signalsreceived from the sensor unit 2 before transmitting the movement signalsto a receiver unit 5. The receiver unit 5 may be of any type known tothose skilled in the art, and useful for receiving data from the sensorunit and making it available to a clinician, physician or technician oncomputer device 6. The computer device 6 will be referred to as a tablet(or tablet computer), but it is meant to be understood that it may beany such similar device, including, but not limited to desktopcomputers, laptop computers, tablet computers, personal digitalassistants (PDAs), “smart” cellular telephones, or the like. Thistransmission may be wired, but is preferably wireless, advantageouslyproviding the subject the greater comfort and convenience of beinguntethered as well as endowing the system with enhanced safety andportability. The wireless link frees subject motion, which allowsunimpeded and accurate assessment of subject symptoms. In an operatingroom, a small untethered system has the added benefits of reducingfurther subject discomfort and not impeding clinical traffic. A wirelesssystem, which is not directly connected to any source of AC power, hasthe added benefit of reducing or eliminating risk of electrical shock.Preferably, the wireless transmission is robust and operates in afrequency band designated for hospital or clinical-setting use.Preferably, the wireless transmission radio is a Bluetooth radiooperating in the 2.4 GHz band. More preferably, radio transmissionoccurs over the Wireless Medical Telemetry Service (WMTS), dedicated bythe FCC to wireless medical equipment used in hospitals, which comprisesthe frequencies 608 to 614 MHz, 1395 to 1400 MHz and 1429 to 1432 MHz.Preferably, radio communication is accomplished using a mix oftraditional heterodyning techniques along with newer software radiotechniques. For example, receiver structure consists of a band selectfunction of either 608-614 MHz or 1395-1432 MHz, followed by aheterodyning operation. The lower frequency band undergoes one frequencytranslation while the upper undergoes two frequency translations. Forthe low band (608-614 MHz) the signal is translated to 44 MHz where itis then sampled by an A/D converter and demodulated in the “sampled”domain. The high band is translated first to the lower frequency band(608-614 MHz) and processed in the same fashion. The software radiodemodulation approach accommodates many different data rates andmodulation formats and advantageously allows future radio upgrades to beimplemented simply by changing the signal processing program opposed tonecessitating an entire analog hardware redesign. The low band transmitsignal is a simple frequency source modulated with appropriateinformation. For the high band transmit signal, the same signal used forthe low band transmit signal is mixed with a high frequency signal toproduce the desired output. For transmitter operation, the signalprocessing hardware generates the modulating signal for all differentsignal formats and data rates. The signal processing hardware outputs amodulating signal input to an oscillator circuit that creates themodulated transmit signal. The modulated signal, for the high band, usesthe low band modulator and translates that signal to the properoperating frequency. Since the modulator is the same for both low andhigh bands it ensures the same signal quality regardless of operationband. Since the radio is a transceiver (two-way link), the design canserve as a master or slave; thus the same design can be employed in thecommand module 3 as well as in the receiver unit 5.

Data may also be collected in an on-board memory contained within thecommand module 3. Such onboard or internal memory may be used fortemporary storage so that the data may be saved and then downloaded tothe tablet computer 6 later, advantageously allowing the subject to wearthe movement disorder diagnostic device comprising sensor unit 2 andcommand module 3 for more prolonged symptom monitoring. Additionally, orin the alternative, the onboard memory may be used to temporarily storethe movement data and provide a backup in the event of halted,corrupted, or otherwise incorrect transmission of the data from themovement disorder diagnostic device comprising sensor unit 2 and commandunit 3 to the receiving unit 5.

The receiver unit 5 may be, and is preferably integrated into somelarger system—for example, it may consist of a wireless receiver, suchas a Bluetooth receiver, integrated into a device such as a laptop ortablet computer, a cellular phone, etc.—or it may be a separate devicebuilt into an enclosure. However, in the illustrated embodiment, thereceiver unit 5 is connected to a tablet computer 6 via one of the USBports (not shown, in a dongle-style connection that advantageouslyeliminates a cable), is powered thereby, and comprises a radio frequencytransceiver capable of 2-way radio frequency communication with thecommand module 3. Power regulation and USB-based data transmissionprotocols may be among any known in the art. The receiver unit 5 may be,in some embodiments, an off-the-shelf Bluetooth USB adapter dongle.

The tablet computer 6 is used to collect data transmitted from thecontrol module 3, allow user inputs to store and track motor performanceand therapy device parameter settings, and provide clinicians withreal-time symptom quantification feedback. The tablet computer 6 of theillustrated embodiment may be any computing device with a user interface7, including a smart phone, PDA, laptop computer, desktop computer,iPhone, iPad, or the like. Preferably, the tablet computer 6 islightweight and portable, allowing for its easy transport within anoperating room, and includes a touch screen. In some embodiments, thetablet computer 6 may be equipped with a clip or hanger (not shown) foreasy mounting to, for example, an operating room pole.

The user interface 7 may be visual, preferably comprising a touchscreen, or it may be an audio interface that accepts and transmitsspoken commands. In addition, or alternatively, the user interface maybe used to provide an automated testing protocol to the subject 1 byproviding instructions to the subject 1 on which movement disordertest(s) to perform, and how to perform them. In other embodiments, thesubject may be instructed on which tests to perform and/or how toperform them on a separate display, not on the tablet's user interface.The user interface 7 preferably provides several key components and anoverall software wrapper. First, it preferably provides a main menu (notshown) to access all software features including a subject database (notshown), the tuning assistant software, which runs the therapy deviceparameter settings tuning algorithm, and software for automaticallygenerating clinical reports following tuning sessions. Next, itpreferably provides a module to view real-time motion data transmittedby the movement disorder diagnostic device comprising sensor unit 2 andcommand module 3, helping ensure proper setup and communication prior toclinical therapy device programming. The user interface 7 alsopreferably communicates with the system registry to store systemparameters and clinician preferred settings. Finally, a help menu (notshown) with troubleshooting guides and frequently asked questions ispreferably included.

Subject data management is an important aspect of clinically-usedembodiments of the present invention. Preferably, the format of thesoftware used with the system is designed for a high volume subjectdatabase. Any database known in the art may be used but is preferablyone which scales well to accommodate thousands or tens of thousands ofsubjects. Preferably, the database has fields for subject history,including the subject's surgery dates, a running list of the subject'sclinical sessions (past and/or future scheduled), the subject's primaryphysician, neurologist, medication dosage, etc. Preferably, the subjectis also programmed with the ability to import e-mails and otherdocuments into the subject history, and to export a standardized patientinformation sheet (reporting). Preferably, the database is programmed soas to permit all stored subject information to conform HIPAA guidelinesfor patient privacy and confidentiality.

A separate programmer device 8 is used in some embodiments by theclinician, physician or technician to program the subject's therapydevice, that is, to adjust the therapy device's parameter settings. Theseparate programmer device 8 may be a separate device from the tablet 6,but more preferably the tablet is capable of providing both functions.Whether the separate programmer device 8 is separate or integrated, itcommunicates with the subject's therapy device (e.g., DBS device), andtransmits the desired therapy parameters to the subject's therapy devicesuch that the therapy device operates under the transmitted parameters.Where the programmer device or unit is separate from the tablet,preferably communication between them is by wireless methods asdescribed above. In all embodiments, the programmer device or unitpreferably communicates wirelessly with the subject's therapy device.

In addition, or alternatively, the movement disorder diagnostic devicecomprising the sensor unit 2 and command module 3 may transmit to aserver or group of servers constituting a centralized database, such aswith cloud computing whereby the data resides on such server or group ofservers and can be accessed at the point of testing or some remotelocation for review by a clinician, physician or technician. Further,the tablet and/or programmer device or unit may also communicate withand transmit data to a centralized database or cloud-based database inorder to store the preferred therapy parameters for the particularsubject, as well as information regarding the testing and tuningprotocols used to arrive at the desired parameters. All the data that istransmitted and stored on a centralized database or cloud-based databaseis intended to be made accessible to the clinician, physician ortechnician for later review, for reference when the subject requiresadditional treatment or tuning, and to be readily available to otherclinicians, technicians or physicians who the subject may receivetreatment of any variety from and who might need to access the data inorder to properly and safely attend to the subject. For example, asubject may reside in one state through the summer months and receivetuning of the therapy device and treatment there, but then may travel toanother state for winter months and require similar attention there. Thedatabase storage of data allows clinicians, technicians or physicians inboth states to readily obtain access to the subject's data and toprovide the appropriate care to the subject. In all exchange ofinformation that occurs in the above example and in all otherembodiments of the present invention, it is important that informationbe exchanged securely and in ways that do not improperly disclose asubject's identity. Because of this, in certain preferred embodiments,all personal information of a subject is stored securely at a remotedatabase and is accessible only through a secure network connectionwherein both the database and connection protocol are compliant withstandards required by the health insurance portability andaccountability act (HIPAA). Often, this will require encryption of thedata to eliminate the possibility that the data can be read by a thirdparty and many preferred embodiments of the present invention includethe use of data encryption.

As indicated in the above example, various embodiments of the presentinvention involve sending a movement disorder monitoring device home orto another remote location with a subject to be used for movementdisorder testing away from a physician's or clinician's place ofpractice. This step occurs after programming of the display unit asdescribed above. Once the subject arrives home, the movement disordermonitoring device is placed in the subject's home where it may bepowered by either a single or multiple on-board batteries or by anotherpower source in the subject's home such as a standard 120 voltalternating current outlet. Once in the home the display unit will, atintermittent times selected by the programming physician or clinician,alert the subject of the need to perform certain movement disorderevaluation tasks. At these times, the display unit may produce a sound,provide a visual alert on its display screen, or a combination of bothas a way to alert the subject. In response to the alert the subject willplace at least one sensor on his or her extremity(ies) as instructed bythe display unit and will proceed to follow other instructions providedregarding how to properly complete certain tasks used to evaluate theseverity of the subject's movement disorder symptoms. In certainembodiments, the subject may be video recorded by the camera of thedisplay unit so that a physician can at a later time verify that thetasks were indeed correctly completed. Preferably, the subject will alsoanswer other questions at this time regarding a subject'sself-assessment of his or her symptoms and the subject's adherence toand use of treatments prescribed by the subject's physician or anotherclinician. Such questions may consist of inquiries related to thesubject's perception of the present severity of the subject's symptoms,the subject's most recent dose of pharmaceutically-based treatment, thesubject's activity level throughout the day, and other similar pertinentinformation that is desired to be known by the physician to help betterunderstand a subject's symptoms. As noted above, however, in certainother embodiments, the display unit may not be programmed to alert asubject, but instead may simply be left available for a subject to inputdata regarding his or her symptoms or to select movement disorderassessment tasks to perform from among various options according to thesubject's personal preferences and schedule as well as the subject's ownsubjective view of the severity of his or her symptoms.

By way of a more specific example of the above situation, a physician orother clinician may see a subject for treatment of PD and the subjectmay indicate to the physician that his or her symptoms associated withPD vary greatly throughout the day. To better understand the diurnalfluctuations of the subject's symptoms, the physician may program adisplay unit to intermittently alarm over a certain duration of time andto instruct the subject to, for example, wear the sensor on thesubject's right hand while performing hand grasping exercises, fingertapping exercises and to simply wear the sensor for a period of timewhile resting to examine the severity of a subject's rest tremor. Theprogrammed display unit is then sent home with the subject with at leastone accompanying sensor and sensor dock. After arrival at home, thesubject follows the intermittent instructions provided by the displayunit (or records his or her own symptoms according to personalpreference if the display unit is not programmed) and then returns thedisplay unit along with its collected data to the physician's office,allowing the physician to then better understand the subject's symptomsand to more effectively treat these symptoms by taking steps to moreaccurately minimize daily symptom fluctuations.

In still other embodiments, a physician or other clinician may meet witha subject who exhibits symptoms of a movement disorder and, beforebeginning treatment of the subject, send a programmed movement disordermonitoring device home or to another remote location with the subjectwhere the subject uses the device to record his or her symptoms beforereturning the device and accompanying data to the physician or otherclinician. By examining a subject's symptoms before beginning treatment,a physician or other clinician can establish a “baseline” against whichto monitor changes in the severity of a subject's symptoms as treatmentmethods are changed and/or as time passes and movement disorder symptomsworsen or improve.

It will further be recognized that in certain preferred embodiments, itmay be undesirable for a subject to first meet with a physician or otherclinician prior to undergoing movement disorder monitoring using themovement disorder monitoring device of the present invention at a remotelocation. Instead, it may be preferable to directly ship or deliver amovement disorder monitoring device to a subject at a remote locationand instruct the subject to return the movement disorder monitoringdevice upon completion of the assigned monitoring period. In this way,both the subject and the physician can avoid the cost and inconvenienceassociated with a preliminary appointment if it is desirable that asymptom baseline first be established for a subject prior to aphysician's meeting with the subject or if such monitoring is desired tobe conducted to assess, for example, the efficacy of ongoing treatment.

The duration of time during which the movement disorder monitoringdevice may remain in a subject's home or other remote location with thesubject and intermittently provides instructions to the subject and/orallows the subject to “journal” his or her symptoms can vary dependingon the nature of the subject's movement disorder and the specific datadesired by the programming physician or clinician. In certain preferredembodiments, the movement disorder monitoring device may be in asubject's home for a relatively short period of time such as 8 or even 6hours. In still other embodiments it may be desirable that the movementdisorder monitoring device remain in a subject's home or other remotelocation for a period of days. In yet other embodiments, it may bepreferable to have the movement disorder monitoring device remain in asubject's home for a number of weeks. It will further be appreciated bythose of ordinary skill in the art that keeping the movement disordermonitoring device of the present invention in a subject's home for evenlonger periods of time, such as months or even years, may be desired asa way to better understand a subject's symptoms over a greater durationof time and would provide powerful ways to examine trending in asubject's symptoms over a period of months, years, or even decades.

Certain embodiments of the present invention in which longer movementdisorder monitoring times are especially valuable include embodiments inwhich the movement disorder monitoring device is used to monitor asubject's response to treatment directed at stopping or slowing theonset of a movement disorder. Continuous monitoring over times rangingfrom months to years to even decades is advantageous with the use oftreatment directed at stopping or slowing the onset of a movementdisorder because movement disorder symptoms can be very subtle when amovement disorder is in its early stages of development and theobjective information provided by the movement disorder monitoringdevice of the present invention allows a physician or other interestedindividual to accurately and objectively monitor small changes insymptom severity over time. Thus, by allowing monitoring over a longerperiod of time, a physician or other clinician or even researcher coulduse the movement disorder monitoring device of the present invention tocollect objective data regarding a subject's disease progression and,hence, the efficacy of a given treatment at stopping or slowing asubject's disease progression. It will be further noted that use of thedevice and method of the present invention in combination with treatmentdirected at stopping or slowing the progression or onset of a movementdisorder is intended to optionally include the use of the movementdisorder monitoring device with a broad scope of pharmaceutical agentsand/or other treatments directed at stopping or slowing the progressionor onset of a movement disorder. Neuroprotective drugs provide onespecific example of a compound that can be used to stop or slow theprogression or onset of a movement disorder. Briefly stated,neuroprotective drugs include a broad set of compounds that serve toeliminate or reduce neuronal death in the central and/or peripheralnervous systems, hence eliminating certain movement disorder symptomsthat can follow neuronal death and stopping progression or onset of amovement disorder disease. By way of specific example, in the case of PDcertain drugs have been and are being examined and may be found to beeffective at eliminating or reducing death of a subject's dopamineproducing neurons, and the efficacy of such drugs over extended periodsof time could be objectively monitored using the device and method ofthe present invention as a means to collect and review movement disordersymptom data over extended periods of time. By way of example,neuroprotective drugs that have been and are being examined for theirpotential in stopping or slowing the progression of movement disorderssuch as PD include drugs such as selegiline, riluzole and lazabemide. Itis to be understood that the scope of the present invention is intendedto cover the use, with the device and as part of the method of thepresent invention, of these drugs as well as other neuroprotective drugsthat may yet be discovered or are currently under investigation.

It may further be appreciated that just as the device and method of thepresent invention may be used in combination with treatments designed toslow or stop movement disorder onset or progression, the device andmethod of the present invention may also be used to monitor the efficacyof certain restorative treatments. By restorative treatments it is meanttreatments that are directed at restoring the natural function, orpartially restoring the natural function, of the part or parts of asubject's body, the failure of which acts as the source of the subject'ssymptoms. This differs from the other traditional treatments discussedabove, such as administration of levodopa to a subject with PD or givingprimidone to a subject with essential tremor, in that the goal of arestorative treatment is to eliminate dependence on external treatmentof symptoms and instead focus on addressing the source of the problemitself. For example, in many instances such treatment may consist ofgene therapy directed at restoring the function of certain cellscritical to the development and/or symptoms of a subject's movementdisorder. In other instances such treatment could consist ofimplantation of encapsulated cells from an external source, with theencapsulated architecture designed to provide immunoprotection to theencapsulated cells and allow the encapsulated cells to fulfill the roleof the subject's native cells that no longer function correctly. By wayof specific example but not limitation, such treatment may comprise thereplacement of dopamine producing cells in the substantia nigra regionof a subject's brain in a subject diagnosed with PD, using dopamineproducing cells encapsulated to prevent a subject's immune response tothe implantation. In all of the above, it is to be understood that thescope of the use of the device and method of the present invention incombination with treatments directed at preventing or slowing movementdisorder onset or progression or at restoring function of native tissueextends beyond the basic examples provided above and includes all usesand approaches included within the general areas of treatment mentioned.

Various embodiments of the present invention also involve the subjectreturning the movement disorder monitoring device to a physician'soffice or another location after use. The method of return can varydepending on a subject's preferences and/or circumstances. In certaininstances, the movement disorder monitoring device may be returned inperson. In other instances it may be preferable to return the device bymail or courier service. It will be apparent to those of ordinary skillin the art that the movement disorder monitoring device of the presentinvention is further amenable to return by any other method commonlyused to deliver, ship, or transfer items between parties.

Upon return, or prior thereto, to the physician's or clinician's officeor other desired location, the data collected from the subject using themovement disorder monitoring device is preferably transferred from thedevice to a different location for further analysis and review. Transferof the data from the movement disorder monitoring device can occur in anumber of ways including wireless transfer (e.g. IEEE 802.11 orBluetooth as mentioned above) from the device, removal of the devicememory module and subsequent upload to a separate location, and the useof various data exchange and transfer utilities including the internetor other communication system such as a local area network. Portabledata storage devices such as USB flash drives and compact discs can alsobe used to transfer data from the movement disorder monitoring devicefor further analysis and review. It will further be noted that it isoften the case that combination of the above-noted data transfer methodswill be most advantageous.

By way of example, in certain preferred embodiments of the presentinvention, a USB flash drive may be used to initially transfer data fromthe display unit of the movement disorder monitoring device. The USBflash drive can then be plugged into a personal computer or other devicethat has a connection to the internet. The internet connection can thenbe used to transfer data to a remote database where further analysis andreview of data can be performed. In still other preferred embodiments,data transfer may be accomplished by directly connecting the displayunit of the movement disorder monitoring device to the internet such asusing a Wi-Fi connection or a category 5 data cable connection to allowdirect transfer of data form the display unit to a remote database. Itwill be clear to those of ordinary skill in the art that various othermethods beyond the specific examples just provided exist through whichmovement disorder symptom data can be transferred from a device such asthe display unit of the present invention and it is intended that theseother methods be included within the scope of the present invention.

In the embodiment illustrated in FIG. 1, the subject 1 performs amovement disorder test according to instructions. In an in-clinicsetting, a clinician, physician or technician may orally or visuallyinstruct the subject on which test(s) or task(s) to perform, and/or howthey are to be performed. Optionally, and more preferably, theseinstructions may be provided by an instructional video clip displayed onthe user interface 7 of the tablet computer 6, or on a separate displaydevice (not shown) advantageously providing the subject with astandardized visual aid to mirror while a test is conducted and data iscollected. Such a system implemented in software and provided throughuser interface 7 ensures the same clinical examination protocol is usedduring subsequent test or programming sessions either in-clinic or in anon-clinical setting, advantageously allowing clinicians to morerepeatedly and objectively track symptoms and assuring inter-subjectdata correspondence. In one embodiment, testing includes (or may belimited to) three types of tremor tasks (resting, postural, and kinetic)and three types of bradykinesia tasks (finger tapping, hand grasps, andpronation/supination). Either alternatively or in addition, testing mayinclude various gait/balance tasks as well. The movement disorderdiagnostic device, or more specifically the sensor unit 2 of thediagnostic device, collects data, which is sent to command module 3 fortransmission via radio link to a receiver unit 5. The processor of thetablet computer 6 processes the movement data to extract kinematicfeatures, which are then fed into a trained scoring algorithmimplemented as a software algorithm in the tablet computer 6. Thetrained scoring algorithm may output a score, which may then optionallybe displayed on the user interface 7. A tuning algorithm of tabletcomputer 6 then computes suggested therapy device parameters or settingsbased at least in part upon the current therapy device parametersettings and the collected movement data and/or the quantified scorecomputed therefrom. One example of a tuning algorithm for computing thesuggested therapy device parameter settings is illustrated in FIG. 3. Inmany embodiments, the various algorithms utilized are able to analyzethe measured and quantified movement data in correlation to the therapyparameters or settings being provided, determine if those parameters orsettings or causing side effects to occur, and be able to anticipatesimilar parameters or settings that might cause the same side effect tooccur. In such embodiments, the algorithm would then know to avoid theparameters or setting that are likely to cause the side effect, and thusavoid including them in the provided set or group of parameters andsettings.

Once suggested parameter settings adjustments are computed by the tuningalgorithm(s), the adjustments or new parameters or settings mayoptionally be displayed on the user interface 7. The tablet computer 6may communicate directly with the programmer device or unit 8, wired orwirelessly, to adjust the parameter settings. The therapy device may bereprogrammed wired or wirelessly, and typical implanted therapy devicesare enabled with means of wireless transcutaneous reprogramming.

The alternate embodiment of the invention depicted in FIG. 2advantageously combines the receiver unit 5, the tablet computer 6, theuser interface 7, and the separate programming device 8 into aprogrammer unit 9 having improved user interface 10, which is preferablya touch-screen interface. The command module 3 of the movement disorderdiagnostic device transmits movement data acquired by the sensor unit 2of the movement disorder diagnostic device, as described above, to theprogrammer unit 9, where the movement data is analyzed and parametersettings adjustments are computed. The parameter settings may thenautomatically updated, with the programmer unit 9 interfacing with thetherapy device (not shown) directly to reprogram the therapy device'sparameter settings.

Preferably, the touch screens of tablet computer 6 and programmer unit 9permit a user to interact with the user interface 7 or the improved userinterface 10 using a large sterile stylus (not shown), or the user'sfinger.

In alternate embodiments of the invention, quantification of movementdisorder symptoms may be performed using a different form of movementmeasuring apparatus. In one such example, a webcam built into the tabletcomputer 6 or programmer unit 9, or a video camera or set of multiplecameras connected thereto, view the subject 1 performing the motiondisorder test and feed video data into the tablet computer 6 orprogrammer unit 9 where, for example, machine vision algorithms measurethe motion of the limbs of the subject with respect to time according toany method known in the art. Such a method may consist, for example, indetermining marker points along the limb of the subject in order togauge relative motion, and such a method may be assisted by applyingmore visible markers (not shown) on various points on the limb of asubject 1, such as is common with motion capture technology. In suchcase, the need for the movement disorder diagnostic device comprisingsensor unit 2, with its accelerometers and gyroscopes, and commandmodule 3, may be obviated.

In one embodiment, an initial programming session will be carried outwhen the device is first provided to the subject according to a protocolcomprising the following steps. The clinician will assess all motor taskbaseline scores. The clinician will check electrode impedance for wiredamage. The clinician will record medication dosages, which informationpreferably includes information relevant to the subject's present levelof medication, such as time and dosage of last medicationadministration. The clinician will select programming motor tasks, andin conjunction with the programmer device or unit 8, 9, the subject willrepeat the series of motor tasks for each stimulation setting. The DBSsettings or parameters and corresponding scores for each chosen motortask will then be entered preferably automatically by the system, andwhere the clinician has the ability to switch between tasks for enteringdata and selecting which DBS parameters are fixed: frequency, current,pulse width, waveform type, contact setup (mono, bi, tripolar), and thelike. Finally, the tuning algorithm(s) will assess all motor taskspost-programming, and the clinician will have the option of reviewing,and possibly editing the resultant parameters or settings. Preferably,for the clinician's optional review and editing, the system will providethe ability to enter DBS settings or parameters and scores completelyeither with a finger or stylus on a touch screen, and/or with a mouseand/or with a keypad or keyboard using the tab key to switch betweendata input fields. Preferably, the system provides three data inputmodes for clinician review and editing: (1) enter stimulation and scoreinformation, click update, enter next measurement; (2) enter informationand display updated tuning map; (3) use stylus/finger/mouse to click onthe tuning map for the appropriate measurement, with a new input boxappearing to enter score/side effects/notes. Optionally, the initialprogramming session may be performed without direct interaction with thetuning map, but rather where the algorithm(s) populate the tuning map,and the clinician, physician, or technician engages the optional reviewfunction to view the tuning map and/or the parameters or settings chosenby the algorithm(s) in order to approve or deny them based on thesubject's needs and the results from those therapy settings.

It is advantageous in some embodiments for the system to provide, or topermit the clinician performing the programming session to enter a largenumber of variables in order to provide a complete assessment of the DBStuning. The following is a representative list of information that maybe entered in each programming session: (1) general subject information,including patient ID, whether the subject's DBS implant is unilateral orbilateral, implant electrode site location and side; (2) motorevaluations performed during tuning, including (a) tremor: rest,postural, kinetic, (b) bradykinesia: finger tap, hand grasp,pronate/supinate, (c) rigidity: elbow/knee, head/neck, (d) leg agility:heel tapping, (e) rising from chair: with arms crossed, (f) posture, (g)gait: walking quality, (h) postural stability: pull back; (3) motorscores, in the form of integer scoring from 0 (no severity) to 4(extremely debilitating); (4) DBS settings or parameters, including, butnot limited to (a) contact: cathode/anode, monopolar, bipolar, tripolar,multiple channels with fractionalized control, waveforms, currentsteering, different waveforms, interleaving multiple waveforms, etc.,(b) stimulation parameters including amplitude (in volts), frequency (inHz), current (in amps), pulse width (in microseconds), the type ofwaveform of the stimulation impulse, (c) side effects and/or capsuleeffects, including (i) motor effects, such as worsening of symptoms,dyskinesias, facial pulling, (ii) non-motor effects, such as blurryvision, soft or slurred speech, sweating, headache, tingling(transient/non-transient), fatigue, sense of euphoria, paresthesia,and/or (iii) new or atypical side effects and update list of notableeffects.

FIG. 3 shows merely one optional example of a tuning algorithm used forcomputing suggested parameter settings adjustments. This basic tuningalgorithm utilizes symptom severity data, detected stimulation induceddyskinesias (SID), and clinical inputs such as clinician definedimprovement percentage (CDI %) to compute suggested stimulationparameter settings. Based on the typical clinical description, severalconstraints reduce the number of degrees of freedom in the tuningalgorithm. During DBS programming, the clinician or the algorithm mayutilize any subset of the motor task mentioned previously to evaluatemotor performance. The average tremor score (ATS) is computed for theset of tremor tasks and the average bradykinesia score (ABS) is computedfor the set of bradykinesia tasks utilized for a given iteration. Thisreduces the number of symptom severity outputs from a maximum of threeto one for each symptom. Dyskinesia is either “on” or “off.”

Recording symptom severity before the therapeutic device is turned onobtains baseline. In the case of DBS adjustment, the best monopolarelectrode contact is determined by finding the contact that provides thelargest therapeutic width, i.e., the largest change in supplied voltagefrom when a clinical benefit is noticed to when side effects occur. Thisis accomplished by fixing stimulation pulse width to initial settings,for example 60 vs, frequency to 130 Hz, selecting one contact, and thenstepping the voltage amplitude in small increments of approximately 0.2V. The procedure is repeated for each contact. The contact that providesthe largest therapeutic width is selected. With the pulse width (60 s)and frequency (130 Hz) set to typical values, the clinician or thealgorithm then sets the amplitude to the lowest voltage that provides asignificant decrease in symptoms. If a satisfactory result is notachieved, pulse width or frequency may also be increased. This can be atime consuming iterative process that must be completed several timesover the first few months as microlesioning heals and requires acompensatory increase in stimulation amplitude to maintain clinicalbenefit. In various embodiments, the invention includes a sensitivetool, implemented in software and accessed through user interface 7 orimproved user interface 10 to detect the instant of clinical benefit asvoltage amplitude is increased and the instant any stimulation induceddyskinesias are detected. Use of the invention as a sensitive measure ofclinical benefit onset and side effect occurrence advantageously ensuresthe contact with the greatest therapeutic width is selected.

Once the contact width is selected, the initial parameter settingsadjustment iteration may be completed with literature-defined settingsof 60 μs and 130 Hz stimulation. Amplitude is set to 0.2 V initially,and then modified by the clinician or algorithm in subsequentiterations. After each stimulation parameter change, the clinician mayuse the user interface 7 or the improved user interface 10 to guide thesubject through motor tasks, or, in some preferred embodiments, thedevice will automatedly provide instructions to the subject via adisplay to provide such guidance. The tuning algorithm output provides asuggested parameter direction output after each motor task evaluation byutilizing the movement disorder quantification algorithm. The inventionthereby maximizes clinical benefit by minimizing tremor andbradykinesia, minimizes adverse effects of stimulation-induceddyskinesias, and minimizes current consumption to maximize battery life.Thus, one objective function is to minimize the sum of average tremorscore (ATS) and average bradykinesia score (ABS), known as the summedmotor score (SMS) 11. This objective is achieved in the tuning algorithmby continuing to increase stimulation in the same direction as long asSMS is decreasing. A higher SMS corresponds to worse motor symptoms. Asecond constraint is that stimulation induced dyskinesias (SID) shouldnot occur. If they are detected, the direction of the parameter changeis reversed. Another system constraint is the minimization currentconsumption. This is accomplished by allowing a clinician definedimprovement percentage (CDI %) 12 and considering any changes of lessthan 5% in SMS to be insignificant. When these conditions are met, thecurrent parameter level is maintained 13 due to the SMS goal beingachieved and with consideration given to diminishing clinical returns,in order to maximize battery life. Once optimized amplitude has beenachieved or reaches 3.6 V, the clinician may adjust pulse width orfrequency utilizing the same algorithm. The chances of the feedbacksystem settling into local minimums are reduced by ensuring several ofthe settings are set at clinically accepted levels for the initialiteration and making only moderate adjustments as required.

While DBS programming frequently entails stepping through smallincremental changes, this process can be wastefully time-consuming ifthe motor symptom response of the subject indicates larger changes arerequired. The implementation of an artificial neural network 14 tooutput suggested stimulation parameters minimizes programming iterationsto reduce surgical and outpatient tuning session time.

Preferably, the artificial neural network 14 used in the tuningalgorithm used by some embodiments of the present invention is trainedwith recorded clinician-made stimulator parameter changes in response tomotor symptom severity changes during stimulator programming to minimizerequired iterations while still utilizing objective symptom severitymeasures to optimize performance. In this way, the algorithm takesclinician experience into account. Experienced clinicians are generallysuccessful in quickly reducing the number of potentially successfulparameter settings for tuning DBS systems. An expert clinician iscapable of recognizing severe motor symptoms and modifying a parameterby a larger magnitude, then when the symptom is less and onlyfine-tuning is required. The present invention is therefore capable ofquantitatively detecting motor symptom severity and suggesting aparameter change that approximates or mirrors the parameter change thatwould be made by an expert clinician.

Artificial neural network 14 may be implemented, for example, with theMATLAB Neural Network Toolbox offline using resilient backpropagationbatch training. Inputs to the neural network may include current andprevious stimulation settings 15 and motor responses.

FIG. 4 illustrates a two-layer network structure consisting of onehidden layer 17 with four neurons using “tansig” transfer functions andone output layer 18. As neural networks may fall into local minimumswhen being trained, each network is preferably trained three times withrandomized initial weights and biases and the best training results areselected. Additionally, early stopping improves network generalization.Data is separated into training and generalization sets to ensuretrained networks produce accurate results both when the training set isreapplied and also when it is generalized to new data. Preferably,training data is collected from multiple patients. To ensure that thesystem generalizes to new patients, network generalization can be testedby training the system using a jackknife “one left out” method. Usingsuch a method, the neural network is trained using data from, forexample, only nine of ten subjects. Data from the nine subjects in thetraining set is then reapplied to the trained network to ensure goodcorrelations while data from the “left out” subject is used to testgeneralization. The method is repeated, leaving out each subject onetime. For each training and generalization set, both the mean squarederror (MSE) and R-squared values between the clinician-made stimulatorparameter changes and those output by the system for each stimulationparameter are calculated. The MSE and R-squared for all training andgeneralization sets are averaged.

Preferably, the system achieves normalized MSE values of less than 10%and R-squared values of greater than 0.8 to show substantial agreementbetween system-suggested simulation parameter changes and clinician-madestimulation parameter changes.

Preferably, separate data sets and acquired, and separate neuralnetworks are trained, for the surgical and outpatient scenarios.Preferably, the data used to train the algorithm averages the experienceof multiple expert clinician programmers.

Preferably, the tuning algorithm comprises a neural network asillustrated in FIG. 3, but it might instead or in addition comprise oneor more of adaptive continuous learning algorithms, linear quadraticGaussian control, Kalman filtering, and model predictive control.

When the tablet computer 6 is connected to the Internet or similarcommunications network, wired or wirelessly, it may therefore transmitsubject data to remote systems, allowing general practitioners toconduct DBS programming remotely, minimizing travel for a subject 1 wholives far from a DBS implantation center or suitable programming clinic,so long as the subject 1 is equipped with the movement disorderdiagnostic device comprising sensor unit 2 and command module 3 andmeans of programming and/or making parameter settings adjustments to hisor her therapy device (including DBS implant).

FIG. 5 depicts a series specific display pages corresponding toreporting score provided for optional or periodic review by a clinician,physician or technician in various embodiments of the present invention.These examples of methods of reporting scores with visual displaysassociated with each display stage of the test process are merelyexemplary, and many variations of the display method, as well as thelabeling of the display, are envisioned. One example of displaying ascore for optional or periodic review is the expandable menu view 19,where the user (i.e., clinician, physician, or subject performingself-testing away from the clinician) is presented with a list of thedifferent types of movement disorders or movement disorder symptoms,which may or may not have been measured in a given test. In theportrayed example of this expandable menu view 19, the movement disordersymptoms that may be selected include tremor, bradykinesia, rigidity,gait and/or balance disturbances, and the like. The user is then giventhe option of expanding the results for each of those movement disordersor movement disorder symptoms through a series of levels (i.e., handthen to left or right), in order to view the score that was determinedfor each particular disorder or symptom in the indicated portion of thesubject's body. By way of clarification and example, the subject shownin menu view 19 received a score of 1 during rest for the symptom oftremor in the left hand, and a 2 for the pronation/supination task forbradykinesia in the left hand.

Another optional review display method, which may be independent or usedin conjunction with the expandable menu view is the tuning map 20. Atuning map 20 is generated for each task that the subject is directed toperform, symptom, or side effect and depicts the severity of thesymptoms measured in each sensor that is used for the given task. Eachtask, symptom or side effect that is performed may be represented on adifferent tab (i.e., tab A, tab B, tab C, where the lettered tabs inFIG. 5 either correspond to a task, symptom or side effect).Alternatively, the tab letters may be replaced by other labels orindicators, or even the name, or abbreviation thereof, of the task,symptom or side effect. Further alternatively or in addition, thedifferent tabs may represent combinations of tasks, symptoms (e.g.,averaged results of multiple symptoms), and/or combinations of sideeffects. In this particular embodiment, the amplitude 21 at which thetest was performed is measured in volts and indicated on one verticalaxis of the tuning map 20. Also in this particular embodiment, thecontact being used to provide therapy or stimulation is indicated on thehorizontal axis 23. However, in many embodiments, the axes may representany other test parameter or setting used, and in some preferredembodiments, one of the axes (typically the horizontal) may representdifferent groupings (see FIG. 6) of test therapy settings or parameters.In such embodiments, for example, the axis would provide arepresentation of a group (e.g., 1 representing group 1), which wouldcomprise a predetermined set of therapy parameters or settings beingtested, where the grouping may include variations of any of the abovedescribed therapy parameters or settings, such as contact, current,frequency, waveform, polarity, pulse width, and the like, as well ascombinations thereof. Some embodiments further allow the condition touse varying or comparative settings within the groupings. For example,it may be decided to combine the settings in such a manner to provideweighted scores where one symptom, task, or side effect is given agreater weight than another, but they are combined to create a singleweighted map. Similarly, therapy settings or parameters may be graduallyincreased or decreased as symptoms are continuously measured, ratherthan providing measurements or assessments at discrete amplitude levels.This allows a greater degree of freedom and versatility in defining thetest settings instead of being limited to one or two test parameters pertest. Such groupings decrease the amount of testing time required fortuning, and thus reduce cost to the subject or insurance company, aswell as opportunity cost of the clinician's time spent with a singlesubject. The calculated or estimated score 22 is depicted on a verticalaxis of the tuning map 20 as well, and is indicated as variouscross-hatch patterns. Alternatively, the score may be represented bycolors, shapes, or any other indicator. Each individual box that isshown represents a test performed 24. Preferably, the tuning map 20 isshown on a color display (not shown) for optional review and theseverity of the symptom is indicated by color. In this drawing, thecolors are represented by different types of shading or cross-hatchingrather than by the preferred color. Each column in the tuning map 20represents a different contact on the DBS probe. Therefore, eachindividual test box 24 depicts the results of performing a task whileadministering DBS at a prescribed voltage amplitude 21 and provides botha severity of the symptom that was detected or measured by virtue of thecolor (represented by the cross-hatching), which also correlates to agiven motor score. Additionally, each individual test box 24 may beselected, for example by pressing it on a touch-screen device, asrepresenting by the test boxes 24 which are outlined in black. When atest box 24 is selected, the user is able to see a detailed view (notshown) of the statistics and parameters of the test corresponding tothat box. In many embodiments, the clinician, physician or technicianmay be able to add notations to the different parameter or settinggroupings, or even to the individual test scores. Such notations mayinclude commentary or other notes regarding the efficacy of the givenparameter grouping or score, of side effects that occur, or any othernotations the clinician, physician or technician deem necessary.

A variable window 25 may display on the unit as well that allows theuser to input various conditions that have an effect on the test andtest results. These variables are calculated into the test results andhelp to give a more accurate calculated symptom score.

Other methods of displaying data corresponding to test therapy settingsor parameters and results may also be envisioned and are considered foruse with the present invention.

FIG. 6 portrays one example of the optional or periodic review tuningmaps 20 or other visual display tool or method for a particularembodiment with amplitude 21 on the vertical axis and groupings ofparameters or settings 23 on the horizontal axis, in greater detail.Each task performed, symptom or side effect is represented again by aseparate tab with its own tuning map 20. Though the tabs are labeled asA, B, C and A+B in the figure, in many preferred embodiments the tab maybe labeled with a number, the name of the task, symptom or side effectit represents, an abbreviation thereof, or some other label indicatingto the clinician, physician or technician what information isrepresented in the given tab. The amplitude 21 of the voltage at whichthe test was performed is tracked along one vertical axis of the map 20for each grouping of parameters or settings 23 on the DBS lead (for thisparticular depicted embodiment), while the severity of the symptomdetected or measured is displayed as a score 22 and correlated to anindicator (e.g., cross-hatching pattern, color, or the like) of eachindividual test result box 24. Again, in many preferred embodiments,rather than the labeling the groupings of parameters or settings 23 usedto provide stimulation with letters (e.g., W, X, Y, Z in the figure),they may instead be labeled by a grouping number, grouping name, or anyother labeling scheme or plan, which indicates to the clinician,physician, or technician which grouping of settings or parameters isrepresented. Preferably, the groupings are cross-referenced within thesoftware and/or GUI such that a user, clinician, physician or technicianmay readily and easily be able to see what parameters or settingscorrespond to the chosen grouping label. The right side 26 of FIG. 6portrays a new tab 27, which represents the combination of tabs A and B.This combination tab 27 represents the combination of the tuning mapsfor tasks A and B, and the combination can be of any mathematicalvariety such as averaging, weighted averaging, or the like.

The combination 27 is a result of the user selecting those two tuningmaps to be combined together and optimized in some mathematical way(e.g., averaging) in order to show the results of how the scores foreach task combine in order to optimize the DBS level for treating thesubject. In other words, the goal is to minimize the voltage at whichthe DBS is to be supplied while simultaneously minimizing the severityof the subject's symptoms and/or side effects. Combining the tuning mapsfor each task allows the user to see a resulting score and select theDBS test parameters, which are as close to optimal as possible. In apreferred embodiment, the system would be designed to be a closed-loopsystem, (i.e., for an implanted home-diagnostic and therapeutic device),which would not require extensive, or any, user input, but would performthe optimization automatically.

FIG. 7 depicts the screening process for determining whether a subjectis a good and viable candidate for DBS therapy. When a subject begins toexperience side effects 35 from medication he or she is taking to treatthe symptoms of a movement disorder, the subject or his or her clinicianmay begin to consider new treatment methods other than simply relying onmedication. The clinician may then have the patient undergo a homescreening assessment 36 to perform monitoring and recording of thesubject's symptoms and test results (motor and cognitive tests) with asystem for monitoring and recording those results. Next, preferably thesystem utilizes predictive tuning algorithms 37 to analyze the manyvariables and test results in order to make a determination as towhether the subject would benefit from DBS therapy 38. If thedetermination is that the subject would benefit, then the clinician andsubject may decide to undergo DBS surgery and therapy 38. However, ifDBS is not a viable option for the subject, then alternative therapies39 should be considered.

FIG. 8 depicts a method of the present invention utilizing an automatedand intelligent DBS (or other therapy) training system. As the subject40 performs motor and cognitive tests, as instructed via a display 42(automated), while wearing the movement disorder diagnostic device 41,the system records and analyzes the results of those tests in light ofthe many variables. The system then populates a tuning map 45, in thebackground, to show the subject's response to the tested DBS (or othertherapy) parameters for each symptom while simultaneously entering thesame data into a tuning algorithm(s). As noted herein, the axes 43 ofthe optional or periodic review tuning map 45 may represent a singletest variable, or may represent a grouping of therapy settings orparameters that are used while the subject 40 conducts a movementdisorder test(s). The tuning map 45 is populated by scores 47representing the severity of the subject's 40 symptom or side effect, orsome other metric being measured, and the same data is entered into thetuning algorithm(s). The tuning map 45 also helps to map the side effectregions, as well as therapeutic and non-therapeutic regions for optionalor periodic review. The tuning algorithm then determines, based on thetest results, a set of therapy settings or parameters that are thenentered into the subject's therapy (e.g., DBS) device for furthertesting or for delivering treatment and therapy to the subject.

FIG. 9 illustrates the difference between (a) monopolar and (b) bipolarDBS lead configurations and the ability to activate desired brain areaswhile avoiding others by shaping the electrical stimulation field. Whileonly mono- and bipolar configurations are depicted, other configurationsare envisioned for use with the present invention as well. A monopolar(a) configuration provides electrical stimulation in all directions fromthe given contact, and that stimulation dissipates as it radiates outfrom the contact. Bipolar (b) configurations simultaneously provideelectrical stimulation from 2 contacts, and depending on the parametersused, can thus alter the shape of the electrical stimulation field. FIG.9(a) shows a monopolar configuration, which provides electricalstimulation in all directions. Thus, with a monopolar configuration, thestimulation provided activates the desired portion 56, which correspondsto the area of the subject's brain which causes occurrence of a movementdisorder symptom, but also activates a side effect region 55, whichcauses a side effect to occur. However, with a bipolar configuration, asin FIG. 9(b), the electrical field may be shaped in such a manner so asto activate the desired region 56 corresponding to a symptom and thustreat that symptom, while avoiding the side effect region 55 and thusavoid causing the side effect to occur.

FIG. 10 depicts an exemplary embodiment of a device that can be carried,attached to, or otherwise readily used by the subject. The device 70 canbe any variety of interface devices, such as a cellular or smarttelephone, PDA, tablet, or the like. In the particular embodimentdepicted, the subject can view the device 70 and view, determine andselect the type of activity, action or task 78 he or she is about toperform or is performing. The activity list 78 depicts any number ofactivities, actions or tasks 78, such as activities of daily living thatthe subject may perform at various points in his or her day. When, forexample, the subject knows he or she is going to go for a walk, thesubject can merely select the walking activity, and the device 70 wouldthen communicate a set of predetermined therapy settings or parametersto program the subject's therapy device (such as an implanted DBSdevice). The therapy device would then operate under the newlyprogrammed therapy settings or parameters. The predetermined settings orparameters may be determined and programmed into the device by aclinician, physician or technician before the device is provided to thesubject. Alternatively, the system may automatedly and intelligentlydetermine preferred settings or parameters based on the activity, actionor task being performed, and the measurements acquired while performingsaid activity, action or task 78. This automated setting or parameterdetermination may initially be based on past performances of the electedactivity, action or task 78, but real-time measurements during eachperformance of the activity, action or task 78 may allow for real-timesetting or parameter needs to be determined and communicated from thedevice 70 to the therapy device. Thus, whenever the subject selects adesired activity, action or task 78, the device would automaticallyreprogram the subject's therapy device to provide the appropriatesettings or parameters to most effectively allow the subject to performthe elected activity, action or task 78.

Particularly in the intelligent, automated parameter or settingdetermination embodiments, the subject may be given the option to definea new activity, action or task 82. Such capability would allow thesubject to perform a new activity, action or task that he or she has notdone before, or to create a new level of a previously defined activity,action or task (such as creating a different activity, action or task 78in the activity list 74 for mowing the lawn and gardening, as opposed tojust yard work, as depicted by way of example in the figure). It may bepreferable, for some subjects, to only allow a clinician, physician ortechnician to define new activities, actions or tasks in which case thisfeature would either be disabled or removed from the interface or device70. In any event, the automated, intelligent programming systems wouldallow the device 70 to take real-time measurements of the subject'smovements, analyze the movement data, and determine the best therapyparameters or settings for maximizing the subject's ability to performthe activity, action or task. This maximization of the subject's abilityto perform the activity, action or task may correspond to a minimizationof symptoms, a minimization of side effects, a combination thereof, orany other combination of possible desired results or outcomes describedherein as they pertain to the particularly elected activity, action ortask.

Optionally, the device 70 may provide the ability to view and review thesettings for an elected activity, action or task 76. The subject or aclinician, physician or technician may simply select a button 80corresponding to the settings for a particular activity, action or task,and the therapy parameters or settings would be displayed for review.Depending on the embodiment or the person reviewing the settings, thisoption may also provide the ability to manually edit the prescribedsettings for a particular activity, action or task. Preferably, theability to edit the parameters or settings is available only to aclinician, physician or technician. The subject may be able to view thesettings in order to take notes or to discuss the settings with theclinician, physician or technician while at a remote location such as athome. In light of the various features of the device that upload andstore the parameters and settings in a database, either in real-time oron-demand, the activity settings are similarly reported and stored forremote (in time, location, or both) access.

FIG. 11 depicts a flow chart representing a method embodiment of thepresent invention for tuning the movement disorder diagnostic devicewith new therapy parameters or settings. This particular embodiment isenvisioned to be performed in an automated fashion, by an algorithm(s),with little or no interaction required with a clinician, physician ortechnician. First, a movement disorder diagnostic device is provided toa subject 90 who has a therapy device, such as a DBS therapy device. Themovement disorder diagnostic device is as described herein, butpreferably comprises at least one physiological or movement sensor formeasuring the subject's external body motion, or some otherphysiological signal of the subject, where the sensor(s) has a signalrelated to the subject's motion or other physiological signal.Preferably, the movement disorder diagnostic device is a single unit,though may be multiple units (e.g., separate sensor unit andcommand/transceiver module), and is adapted to be worn or attached to aportion of the subject's body such that the sensor(s) of the movementdisorder diagnostic device are able to measure the movement of thatparticular portion of the subject's body.

Once the movement disorder diagnostic device has been provided 90 to thesubject, and the subject has donned or attached the device, the nextstep is to instruct the subject 92 to perform at least one movementdisorder test(s) while the subject is undergoing therapy from thetherapy (e.g., DBS) device, or is under the effects of recentlyadministered therapy therefrom. These instructions may include a list ofwhich test(s) the subject is to perform, directions on how to performthe test, or a combination of both. The instructions to perform a testor tests may be given 92 in person (if in a clinical setting) by aclinician, physician or technician, or more preferably may be providedin an automated or electronic fashion. For example, the instruction toperform the test(s) may be provided automatedly to the subject via avideo display, or a notification or alert message provided via such adisplay or perhaps the subject's smart phone, or the like. Theinstructions are provided 92, either audibly, visually, or a combinationthereof. The subject's performance of the tasks is thus affected by thetherapy being provided, or recently provided by the therapy device.

While the subject is performing the at least one movement disordertest(s) as instructed 92, the step of measuring and quantifying motorsymptoms 94 of the subject based at least in part on the signal of theat least one sensor(s). The movement disorder diagnostic device uses thesignal of the at least one sensor(s) to provide an objective measurementand quantification of the severity of the subject's motor symptoms whilethe subject performs the at least one movement disorder test. Themeasured and quantified motor symptoms may include specific movementdisorder symptoms, side effects from medication and/or therapy, orcombinations thereof. The trained scoring algorithms of the movementdisorder diagnostic device perform various measurements and calculationsto provide this objective quantification of the subject's motorsymptoms.

Once the subject's motor symptoms have been measured and quantified 94,data corresponding to these measured and quantified motor symptoms isentered into an algorithm(s) 96 for automated analysis. Typically, thedata corresponding to the measured and quantified motor symptoms is anobject score, as described herein, but may be represented in numerousways and means. Preferably, the quantified movement data is entered 96directly and automatically into the determination algorithm(s) withoutthe need for any manual human intervention, such as keying in the data.

The determination algorithm(s) then analyze the quantified movement dataand determine a second level of therapy parameters or settings 98. Thissecond level of parameters or settings preferably corresponds to a modeof therapy or treatment that addresses the subject's needs as determinedbased on the measured and quantified motor symptom data, as well asother data, goals, or objectives. In other words, if the systemdetermines that the subject is experiencing a very strong tremor, suchdetermination being made as a result of the measurement of the subject'smovement and quantifying the severity of the tremor, the algorithm wouldprovide a second level of parameters or settings 98 that would reduce orminimize the tremor the subject is experiencing. As noted, thedetermination of a second level of parameters or settings may be basedon any number of constraints or desired results for the subject, notsolely the immediate symptom or side effect the subject is experiencing.For example, if the subject's main concern is reducing or minimizingsymptom occurrence and or severity, algorithms will take this desiredgoal into account when determining the second level of parameters orsettings. Similarly, the determination of settings or parameters may bebased on a desired reduction or minimization of side effects frommedication or the therapy. Also, the determination may be made tobalance multiple desired results, such as if a slightly higher rate ofoccurrence of symptoms is acceptable to the subject in exchange for aminimization of side effects. Other examples of desired results that maybe used to determine the second level of therapy parameters or settingsfor all embodiments include, but are not limited to, a therapeuticwindow (in terms of time or some other factor) in which the subject mostpositively responds to therapy, battery life, and other such constraintsthat might be considered in terms of optimizing the therapy parametersor settings. In any determination, the subject and the clinician,physician or technician decide what the initial desired result is, andthese desired results, goals, or constraints are programmed into thealgorithm for the decision making process. In some embodiments, thedesired result, goal or constraints may be edited, either by aclinician, physician or technician, or by the subject, in order to allowthe algorithm to most accurately analyze the data in light of theoptimal treatment for the subject.

Once this second level of parameters or settings has been determined orprovided by the algorithm(s) 98, the parameters or settings are enteredinto the subject's therapy device 100. The parameters or settings arepreferably entered automatically via wireless communication, asdescribed herein, between the diagnostic device or computer and thesubject's therapy device. As such, the new, second level of parametersor settings is programmed into the subject's therapy device, and thedevice then operates according to those new parameters or settings 102and provides that newly determined course of therapy or treatment to thesubject. Thus, the system measures and quantifies the subject's symptoms94, automatically determines a second level of therapy parameters orsettings that would address those symptoms 98, the second level ofparameters or settings is automatically and wirelessly programmed intothe subject's therapy device 100, and the therapy device implements thesecond level of parameters or setting to in fact address the subject'ssymptoms 102.

FIG. 12 depicts a flow chart representing a method embodiment of thepresent invention for tuning the movement disorder diagnostic devicewith new therapy parameters or settings. This particular embodiment isenvisioned to be performed in an automated fashion, by an algorithm(s),with little or no interaction required with a clinician, physician ortechnician. First, a movement disorder diagnostic device is provided toa subject 90 who has a therapy device, such as a DBS therapy device. Themovement disorder diagnostic device is as described herein, butpreferably comprises at least one physiological or movement sensor formeasuring the subject's external body motion, or some otherphysiological signal of the subject, where the sensor(s) has a signalrelated to the subject's motion or other physiological signal.Preferably, the movement disorder diagnostic device is a single unit,though may be multiple units (e.g., separate sensor unit andcommand/transceiver module), and is adapted to be worn or attached to aportion of the subject's body such that the sensor(s) of the movementdisorder diagnostic device are able to measure the movement of thatparticular portion of the subject's body.

Once the movement disorder diagnostic device has been provided 90 to thesubject, and the subject has donned or attached the device, the nextstep is to instruct the subject 92 to perform at least one movementdisorder test(s) while the subject is undergoing therapy from thetherapy (e.g., DBS) device, or is under the effects of recentlyadministered therapy therefrom. These instructions may include a list ofwhich test(s) the subject is to perform, directions on how to performthe test, or a combination of both. The instructions to perform a testor tests may be given 92 in person (if in a clinical setting) by aclinician, physician or technician, or more preferably may be providedin an automated or electronic fashion. For example, the instruction toperform the test(s) may be provided automatedly to the subject via avideo display, or a notification or alert message provided via such adisplay or perhaps the subject's smart phone, or the like. Theinstructions are provided 92, either audibly, visually, or a combinationthereof. The subject's performance of the tasks is thus affected by thetherapy being provided, or recently provided by the therapy device.

While the subject is performing the at least one movement disordertest(s) as instructed 92, the step of measuring and quantifying motorsymptoms 94 of the subject based at least in part on the signal of theat least one sensor(s). The movement disorder diagnostic device uses thesignal of the at least one sensor(s) to provide an objective measurementand quantification of the severity of the subject's motor symptoms whilethe subject performs the at least one movement disorder test. Themeasured and quantified motor symptoms may include specific movementdisorder symptoms, side effects from medication and/or therapy, orcombinations thereof. The trained scoring algorithms of the movementdisorder diagnostic device perform various measurements and calculationsto provide this objective quantification of the subject's motorsymptoms.

Once the subject's motor symptoms have been measured and quantified 94,data corresponding to these measured and quantified motor symptoms isentered into an algorithm(s) 96 for automated analysis. Typically, thedata corresponding to the measured and quantified motor symptoms is anobject score, as described herein, but may be represented in numerousways and means. Preferably, the quantified movement data is entered 96directly and automatically into the determination algorithm(s) withoutthe need for any manual human intervention, such as keying in the data.

In this particular embodiment, the determination algorithm(s) thenanalyze the quantified movement data and determine at least two optionalgroups of therapy parameters or settings 110. These optional groups ofparameters or settings each preferably correspond to a different orseparate mode of therapy or treatment that addresses the subject's needsas determined based on the measured and quantified motor symptom data,as well as other data, goals, or objectives, and each specificallyaddressing a separate need, goal, desired outcome, or constraint. Forexample, the system may detect that the subject is experiencing a highdegree of rigidity along with speech problems caused by the electricalstimulation. In this particular embodiment, the system would provide twooptional groups of parameters or settings 110, one which more directlyaddresses the symptom of rigidity, and one that more directly addressesthe side effect of speech problems. Similar to the second level ofparameters or settings discussed above, the determination of theseoptional groups of parameters or settings may be based on any number ofconstraints or desired results for the subject, not solely the immediatesymptom or side effect the subject is experiencing. In anydetermination, the subject and the clinician, physician or techniciandecide what the initial desired result is, and these desired results,goals, or constraints are programmed into the algorithm for the decisionmaking process. In some embodiments, the desired result, goal orconstraints may be edited, either by a clinician, physician ortechnician, or by the subject, in order to allow the algorithm to mostaccurately analyze the data in light of the optimal treatment for thesubject.

Once the algorithm has determined and provided the at least two optionalgroups of parameters or settings 110, the subject may then select whichof the provided groups 112 use. This allows the user to determine on anas-needed basis which symptoms, side effects, or other constraints arethe most relevant and important to the subject. When the subject makeshis or her selection 112, the parameters or settings of the selectedgroup are entered into the subject's therapy device 112. The parametersor settings are preferably entered automatically via wirelesscommunication, as described herein, between the diagnostic device orcomputer and the subject's therapy device. As such, the new, selectedgroup of parameters or settings is programmed into the subject's therapydevice, and the device then operates according to those new parametersor settings 116 and provides that newly determined course of therapy ortreatment to the subject. Thus, the system measures and quantifies thesubject's symptoms 94, automatically determines at least two optionalgroups of therapy parameters or settings that would address thosesymptoms or other constraints 110, the selected group of parameters orsettings is automatically and wirelessly programmed into the subject'stherapy device 114, and the therapy device implements the second levelof parameters or setting to in fact address the subject's symptoms 116.

FIG. 13 depicts a flow chart representing a method embodiment of thepresent invention for tuning the movement disorder diagnostic devicewith new therapy parameters or settings. This particular embodiment isenvisioned to be performed in an automated fashion, by an algorithm(s),with little or no interaction required with a clinician, physician ortechnician. First, a movement disorder diagnostic device is provided toa subject 90 who has a therapy device, such as a DBS therapy device. Themovement disorder diagnostic device is as described herein, butpreferably comprises at least one physiological or movement sensor formeasuring the subject's external body motion, or some otherphysiological signal of the subject, where the sensor(s) has a signalrelated to the subject's motion or other physiological signal.Preferably, the movement disorder diagnostic device is a single unit,though may be multiple units (e.g., separate sensor unit andcommand/transceiver module), and is adapted to be worn or attached to aportion of the subject's body such that the sensor(s) of the movementdisorder diagnostic device are able to measure the movement of thatparticular portion of the subject's body.

Once the movement disorder diagnostic device has been provided 90 to thesubject, and the subject has donned or attached the device, the nextstep is to instruct the subject 92 to perform at least one movementdisorder test(s) while the subject is undergoing therapy from thetherapy (e.g., DBS) device, or is under the effects of recentlyadministered therapy therefrom. These instructions may include a list ofwhich test(s) the subject is to perform, directions on how to performthe test, or a combination of both. The instructions to perform a testor tests may be given 92 in person (if in a clinical setting) by aclinician, physician or technician, or more preferably may be providedin an automated or electronic fashion. For example, the instruction toperform the test(s) may be provided automatedly to the subject via avideo display, or a notification or alert message provided via such adisplay or perhaps the subject's smart phone, or the like. Theinstructions are provided 92, either audibly, visually, or a combinationthereof. The subject's performance of the tasks is thus affected by thetherapy being provided, or recently provided by the therapy device.

While the subject is performing the at least one movement disordertest(s) as instructed 92, the step of measuring and quantifying motorsymptoms 94 of the subject based at least in part on the signal of theat least one sensor(s). The movement disorder diagnostic device uses thesignal of the at least one sensor(s) to provide an objective measurementand quantification of the severity of the subject's motor symptoms whilethe subject performs the at least one movement disorder test. Themeasured and quantified motor symptoms may include specific movementdisorder symptoms, side effects from medication and/or therapy, orcombinations thereof. The trained scoring algorithms of the movementdisorder diagnostic device perform various measurements and calculationsto provide this objective quantification of the subject's motorsymptoms.

Once the subject's motor symptoms have been measured and quantified 94,data corresponding to these measured and quantified motor symptoms isentered into an algorithm(s) 96 for automated analysis. Typically, thedata corresponding to the measured and quantified motor symptoms is anobject score, as described herein, but may be represented in numerousways and means. Preferably, the quantified movement data is entered 96directly and automatically into the determination algorithm(s) withoutthe need for any manual human intervention, such as keying in the data.

In this particular embodiment, the determination algorithm(s) thenanalyze the quantified movement data and determine at least two optionalgroups of therapy parameters or settings 110. These optional groups ofparameters or settings each preferably correspond to a different orseparate mode of therapy or treatment that addresses the subject's needsas determined based on the measured and quantified motor symptom data,as well as other data, goals, or objectives, and each specificallyaddressing a separate need, goal, desired outcome, or constraint. Forexample, the system may detect that the subject is experiencing a highdegree of rigidity along with speech problems caused by the electricalstimulation. In this particular embodiment, the system would provide twooptional groups of parameters or settings 110, one which more directlyaddresses the symptom of rigidity, and one that more directly addressesthe side effect of speech problems. Similar to the second level ofparameters or settings discussed above, the determination of theseoptional groups of parameters or settings may be based on any number ofconstraints or desired results for the subject, not solely the immediatesymptom or side effect the subject is experiencing. In anydetermination, the subject and the clinician, physician or techniciandecide what the initial desired result is, and these desired results,goals, or constraints are programmed into the algorithm for the decisionmaking process. In some embodiments, the desired result, goal orconstraints may be edited, either by a clinician, physician ortechnician, or by the subject, in order to allow the algorithm to mostaccurately analyze the data in light of the optimal treatment for thesubject.

Once the algorithm has determined and provided the at least two optionalgroups of parameters or settings 110, the subject may then select morethan one of the provided groups 120 use for further therapy. This allowsthe user to determine on an as-needed basis which combination symptoms,side effects, or other constraints are the most relevant and importantto the subject. When the subject makes his or her selection 120, theparameters or settings of the selected group are then combined into asingle set of parameters or algorithms 122 via an algorithm. Thealgorithm may combine the selected optional groups via many optimizationmethods, such as described herein, in order to provide the optimaltherapy parameters or settings for addressing each of the subject'sselected desired results, goals, or selections to the greatest degreepossible. Essentially, this embodiment allows the subject to not simplytake a binary approach and choose one symptom, side effect or constraintover the others, but rather to make minor concessions in severalcategories in order to address more needs, but to a lesser degree. Oncethe subject makes his or her selection of multiple groups, and thealgorithm has performed the necessary optimization and combination ofthe selected parameters or settings into a single group, this new groupof selected and combined parameters or settings is then entered into thesubject's therapy device 124. The selected and combined parameters orsettings are preferably entered automatically via wirelesscommunication, as described herein, between the diagnostic device orcomputer and the subject's therapy device. As such, the new, selectedgroup of parameters or settings is programmed into the subject's therapydevice, and the device then operates according to those new parametersor settings 126 and provides that newly determined course of therapy ortreatment to the subject. Thus, the system measures and quantifies thesubject's symptoms 94, automatically determines at least two optionalgroups of therapy parameters or settings that would address thosesymptoms or other constraints 110, the selected group of parameters orsettings are combined and optimized 122 to address multiple needs of thesubject, the selected and combined group of parameters or settings isautomatically and wirelessly programmed into the subject's therapydevice 124, and the therapy device implements the second level ofparameters or setting to in fact address the subject's symptoms 126.

FIG. 14 is a flow chart depicting one embodiment of a process by whichthe tuning algorithm(s) is used to determine therapy parameters orsettings and program those settings into a subject's therapy device.Like the embodiments described above, data corresponding to measured andquantified motor symptoms is entered into a tuning algorithm(s) 130 forautomated analysis. Typically, the data corresponding to the measuredand quantified motor symptoms is an object score, as described herein,but may be represented in numerous ways and means. Preferably, thequantified movement data is entered directly and automatically into thedetermination algorithm(s) 130 without the need for any manual humanintervention, such as keying in the data.

The determination algorithm(s) then analyze the quantified movement dataand determine a second level of therapy parameters or settings 132. Thissecond level of parameters or settings preferably corresponds to a modeof therapy or treatment that addresses the subject's needs as determinedbased on the measured and quantified motor symptom data, as well asother data, goals, or objectives. In other words, if the systemdetermines that the subject is experiencing a very strong tremor, suchdetermination being made as a result of the measurement of the subject'smovement and quantifying the severity of the tremor, the algorithm wouldprovide a second level of parameters or settings 132 that would reduceor minimize the tremor the subject is experiencing. As noted, thedetermination of a second level of parameters or settings may be basedon any number of constraints or desired results for the subject, notsolely the immediate symptom or side effect the subject is experiencing.Also, the determination may be made to balance multiple desired results,such as if a slightly higher rate of occurrence of symptoms isacceptable to the subject in exchange for a minimization of sideeffects. Other examples of desired results that may be used to determinethe second level of therapy parameters or settings for all embodimentsinclude, but are not limited to, a therapeutic window (in terms of timeor some other factor) in which the subject most positively responds totherapy, battery life, and other such constraints that might beconsidered in terms of optimizing the therapy parameters or settings. Inany determination, the subject and the clinician, physician ortechnician decide what the initial desired result is, and these desiredresults, goals, or constraints are programmed into the algorithm for thedecision making process. In some embodiments, the desired result, goalor constraints may be edited, either by a clinician, physician ortechnician, or by the subject, in order to allow the algorithm to mostaccurately analyze the data in light of the optimal treatment for thesubject.

In this embodiment, the second level of therapy parameters or settingsis then output or displayed for review 134 prior to implementation. Thisis particularly useful for initial programming of the subject's therapydevice, but is also very useful in subsequent or real-time programmingas well. The second level (or selected group, or selected and combinedgroup) of parameters or settings is transmitted from the subject'sdiagnostic device and displayed our output to a clinician, physician ortechnician 134 who can analyze the algorithm-generated settings toensure they are within acceptable safety limits, as well as ensuringthat they do in fact address the needs of the subject. Preferably, thetransmission of the second settings is performed wirelessly andsecurely, particularly where the subject is located remotely from theclinician, physician or technician. The parameters or settings arepreferably displayed visually to the clinician, physician or technician,such as on a monitor or display device. The parameters or settings maybe displayed in any format known to those skilled in the art, including,but not limited to a textual report such as in an email or text documentsent to the care provider, transmitted to a software package thatdisplays the parameters or settings in a particular graphical userinterface, or transmitted to a centralized or cloud-based database wherethe clinician, physician or technician can access them for review. Wherethe parameters or settings are viewed in a software package, the presentinvention is intended to be adaptable or formattable such that theparameter or settings report or transmission may be used in anycommercially available package, or the like.

When the clinician, physician or technician reviews the parameters orsettings, he or she then has the option of approving or denying theparameters or settings 136. The decision to approve or deny ispreferably based on the likelihood that the algorithm(s)' providedparameters or settings will achieve the subject's desired outcome orgoal, and any other constraints that have been elected either by thesubject, or by the clinician, physician or technician in conjunctionwith the subject. If the clinician, physician or technician determinesthat the parameters or settings will not meet the desired results, goalsor constraints, then the settings or parameters are denied 138, and thedetermination algorithm(s) repeats the process of using the measured andquantified motor symptom data to provide another set of therapyparameters or settings 132. This process may be repeated iterativelyuntil acceptable parameters or settings are achieved. Optionally, theclinician, physician or technician may be given the ability to suggeststarting parameters for the algorithm to begin with, thus circumventingthe need for further motor symptom measurement and quantification. Whenthe algorithm(s) are triggered to provide another iteration ofparameters or settings, the above steps are repeated until theparameters or settings meet or achieve the desired end result fortherapy.

When the caregiver determines that the parameters or settings are, infact, likely to meet those goals, then he or she approves the parametersor settings 140, and the second level, selected group or combinedselected group of parameters or settings is entered automatically andwirelessly into the subject's therapy device 142 in the same or similarmanner as described herein. As such, the new, selected group ofparameters or settings is programmed into the subject's therapy device,and the device then operates according to those new parameters orsettings 144 and provides that newly determined course of therapy ortreatment to the subject.

FIG. 15 depicts an operating embodiment of the present inventionbeginning with the initial occurrence of movement disorder symptoms andending with continuing monitoring and treatment or therapy. The depictedembodiment describes a system involving continuous home monitoring suchthat the device operates virtually full-time, monitoring, measuring andanalyzing the subject's movement data continually; however, alternativeembodiments exist that operate similarly, but with part-time oron-demand monitoring, measuring and analysis. In either embodiment, thesubject initially exhibits symptoms of a movement disorder and attendsan appointment with a clinician 160. At the appointment, the clinicianexamines the subject 162, and upon analysis, diagnoses the subject ashaving a movement disorder, and subsequently orders a course oftreatment or therapy 164. At a follow-up visit, the subject may reportthat symptoms fluctuate greatly throughout the day 166, even while onthe prescribed treatment or therapy plan. The clinician then decides toperform in-home continual testing 168 to better determine the severityof the subject's symptoms. Continuous home monitoring 170 begins withthe initial programming 172 of any movement monitoring devices orautomated treatment delivery devices for the subject, or instructing thesubject how to do so. This initial programming may be performedin-clinic or remotely, and may be performed manually or integrated withthe review of a clinician, physician or technician, or may be performedintelligently in an automated or semi-automated process utilizingtrained tuning algorithms. The device, containing at least one sensor,preferably an accelerometer and/or gyroscope of at least three axes, butoptionally another sensor capable of measuring motion, such as an EMG,continually records the subject's movement during activities of dailyliving 174. In addition, the device can include two or more types ofsensors, preferably accelerometers and gyroscopes.

Activities of daily living may include folding laundry, handwriting,eating, dressing, self-care, walking, running, and the like. Optionally,the clinician may order the subject to perform clinical tasks such asfinger tapping, nose touching, or the like, as defined by standardizedscales such as the UPDRS, TRS, and the like, at regularly scheduledperiods. Such movement data would also be continually recorded.

A trained tuning algorithm, preferably incorporated by at least onecomputer processor, analyzes the recorded movement data 176. This dataanalysis may be performed at a scheduled time where the data is uploadedto the algorithm and analyzed, or, more preferably, may be performed inreal time. The algorithm and processor function to distinguish voluntarymotion of activities of daily living or clinician ordered tasks frommovement disorder symptoms and quantify their severity. Preferably thetrained algorithms and computer processor are also in two-waycommunication 178 with a central database 180 or multiple databases madeup of previous patient movement data, disorder histories, treatmenthistories, and the like. Preferably two or more databases are used forreading. Such a database 180 would preferably retain information fromthe current subject for use with future subjects 182 (maintainingsubject privacy and confidentiality at all times) and work with thetrained algorithms and processor to determine a recommended treatmentfor the current subject based on the previous patient data. Thisdatabase 180 could optionally be used as a real-time gateway forproviding updates to the subject's clinician 184 regarding the subject'sstatus.

If the trained algorithms and processor determine 176 that the patientstill suffers from movement disorder symptoms 186, a new course oftreatment or therapy is determined 188 either based solely on thesubject's measured and quantified symptoms, in conjunction with thecentral database 180 as previously described, or a combination of thetwo. If the subject has an automated treatment delivery device, it ispreferably reprogrammed according to the new treatment protocol 190.Preferably, this reprogramming of the subject's device is performedremotely, and in an automated, intelligent fashion requiring little, ormore preferably no interaction from a clinician, physician ortechnician. The movement measuring device then continues to record newmovement data and the process repeats. If the trained algorithms andprocessor determine 176 movement disorder symptoms no longer persist 192then no new treatment is needed, no changes are made 194, and the devicecontinues recording movement data.

FIG. 16 is a flow chart depicting one example of a tuning algorithm usedto determine the therapy parameters or settings that can be programmedinto a subject's therapy device for another iteration of testing or forproviding therapy according to those parameters or settings. Thisparticularly depicted embodiment is merely an example, and many othercombinations of parameters or settings, number of variables and/or stepsare envisioned. First, a set of initial parameters 200 is programmedinto the subject's therapy device. These initial parameters may bepre-programmed, programmed manually or as part of an integrated system,or automatically programmed via an intelligent algorithm. Further, theinitial parameters may define any number of variables or parameters orsettings as disclosed herein to be set while others are altered ormodified through the tuning process. In the depicted embodiment, someinitial parameters or settings include a pulse width (PW) of 90 μs,frequency (F) of 130 Hz, and pulse amplitude (PA) of 0 mA. An amplitudeof 0 mA essentially means that no therapeutic current is being provided,or the therapy is turned off, but is provided as an initial setting tobeing the testing process from which the amplitude is increasedgradually throughout the testing iterations. Once these parameters areprogrammed into the subject's therapy device such that the device canprovide therapy according to these initial parameters or settings, thetuning process may begin by initially increasing the pulse amplitude 202to a first test level provided to the subject, in the figure shown to bean increase of 0.25 mA. As the therapy is provided to the subjectaccording to the initial parameters and the first level of testparameters, the movement disorder diagnostic device (not shown) measuresand quantifies the subject's movement (not shown) in order to determinethe level of symptoms, side effects, and the like that the subjectexperiences while receiving therapy according to the provided parametersor settings. Based on the measured and quantified movement data, thedepicted algorithm first determines whether side effects are occurring204. If side effects occur under the provided therapy parameters orsettings, then the algorithm may determine that using the presentlytested contact may result in persistent side effects, and move on to thenext contact 218 to test and determine whether therapy can be providedin an alternative pattern from the different contacts to avoid the sideeffects.

If side effects do not occur or do not persist from one iteration of thetest to the next, then the algorithm then determines whether thesubject's symptoms have improved 206 as a result of the tested therapyparameters or settings. This determination, too, is based on themeasured and quantified movement data provided by the movement disorderdiagnostic device. If the algorithm determines that the symptoms havenot improved based on the provided therapy parameters or settings, itmay next perform a query to see how many individual parameters orsettings have been tested (i.e., changed individually to determine theparticular parameter's effect on the subject's side effects and/orsymptoms), or how many groups of parameters or settings have been tested214. In the depicted embodiment, the threshold value is eightparameters/settings or groups thereof. Therefore, in the depictedembodiment, if eight parameters/settings or groups thereof have beentested through the depicted process, the algorithm determines whetherthere has been any improvement in the last four changes inparameters/settings or groups 216. If there has been no suchimprovement, then again, the algorithm may move on to the next contact218 in order to try and achieve a therapeutic response from anothercontact that may address the subject's symptoms and/or side effects andother constraints.

If, however, the depicted algorithm determines that a) the subject'ssymptoms did improve under the provided therapy parameters or settings206; b) symptoms did not improve and fewer than eightparameters/settings or groups thereof have been tested 214; or c) atleast eight parameters/settings or group have been tested, but there hasbeen some improvement within the last four iterations 216, then thealgorithm next determines whether the therapy parameters or settings arebeing provided at a maximum value for one of those parameters orsettings 208—in the depicted case pulse amplitude. Pre-determinedparameter or settings limits may be defined to keep the therapy deviceoperating within safe limits in order to protect the subject. If thespecific parameter or setting that is being tested (in the depictedcase, pulse amplitude) has not reached its maximum value, then thealgorithm may again increase the value of that parameter or setting 202and repeat the process. If the maximum value has already been reachedfor the particular parameter or setting, then that variable cannot beincreased any further, and the algorithm determines whether anotherindividual parameter or setting is at its maximum level 210—in thedepicted case frequency. If the frequency has not reached its maximumvalue yet, then the algorithm reduces the amplitude to zero, increasesthe frequency 220 and then again begins the iterative process byinitially increasing the amplitude 202 to provide therapy to the subjectat the new levels of parameters or settings.

If, however, symptoms have shown improvement as a result in the changein therapy parameters or settings, and both of the first two parametersor settings have reached their maximum levels, then the algorithm nextdetermines if yet another parameter or setting (in the depicted case,pulse width) has yet reached its maximum value 212. If all of theparameters or settings desired to be tested have reached their maximums,then the algorithm determines that the tested contact, though close, maynot provide the best course of therapy, and moves on to the next contact218 to begin the process over. If, however, the next parameter orsetting 212 has not reached its maximum value, the algorithm againreduces the amplitude to zero, maintains the maximum frequency, andincreases the pulse width 222 (again, these are exemplary parameters orsettings, and other combinations are envisioned). Once the updatedparameters or settings have been determined, the algorithm again beginsthe process over by slightly increasing the amplitude 202 to provide atherapeutic current according to the new settings, and repeats thetesting process. This decision process is repeated by the intelligentalgorithm until it determines that the best combination of contact(s)and parameters or settings has been achieved, resulting in an optimizedtherapy that takes into account the subject's side effects, symptoms,and/or other constraints.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to the present inventionwithout departing from the spirit and scope of the invention. Thus, itis intended that the present invention cover the modifications andvariations of this invention provided they come within the scope of theappended claims and their equivalents.

What is claimed:
 1. A movement disorder therapy system comprising: amovement disorder diagnostic device comprising at least onephysiological or movement sensor adapted to be worn, attached or held atdifferent locations on the surface of the subject's body and having asignal related to a subject's motion, the movement disorder diagnosticdevice adapted to provide therapy to a subject with a deep brainstimulation (DBS) device operable with adjustable DBS parameters, and tomeasure movement data based at least in part on the signal of the atleast one sensor while the subject performs at least one movementdisorder test, the movement disorder diagnostic device furthercomprising at least one electronic component adapted to collect andtransmit the measured movement data; a processor comprising aquantification algorithm and a determination algorithm, the processoradapted to, at least in part, extract at least one kinematic featurefrom the measured movement data, the quantification algorithm adapted toreceive data corresponding to the subject's measured motor symptoms andthe at least one extracted kinematic feature and to quantify motorsymptoms of the subject based thereon, and the determination algorithmadapted to provide a suggested level of DBS parameters based on a modeof therapy or treatment corresponding to the subject's needs based atleast in part on the quantified motor symptoms; and a tuning outputadapted to interface with the subject's DBS device to provide a secondlevel of DBS parameters for the subject's DBS device to alter thesubject's symptomatic movement and to be entered into the subject's DBSdevice such that the subject's DBS device operates under the secondlevel of DBS parameters, wherein the at least one kinematic feature isselected from the group consisting of peak power angular velocity, peakpower angle, RMS angular velocity, frequency, maximum amplitude, maximumpeak-to-peak amplitude, mean angular velocity, and wavelet parameters,peak power acceleration, peak power velocity, peak power position, RMSacceleration, RMS velocity, RMS position, mean acceleration, waveletparameters, covariance of any of the kinematic features, and standarddeviation over time of any of these kinematic features.
 2. The system ofclaim 1, wherein the quantification algorithm includes and artificialneural network, a Bayesian network, and/or a genetic algorithm.
 3. Thesystem of claim 2, further comprising a data output comprising datacorresponding to the subject's measured and quantified motor symptomsand/or the suggested DBS parameters, the data output adapted to bedisplayed visually for review by a clinician, physician, or technicianto determine the second level of DBS parameters for the tuning outputbased on the data output.
 4. The system of claim 3, wherein the dataoutput is adapted to be displayed in the form of a tuning map that is atwo-dimensional representation of a three-dimensional graph.
 5. Thesystem of claim 4, wherein the suggested level of DBS parameterscorresponds to a quantifiable decrease in the severity and/or occurrenceof at least one motor symptom, the quantifiable decrease being about 25%or greater.
 6. The system of claim 4, wherein the suggested level of DBSparameters corresponds to a quantifiable decrease in the severity of atleast one side effect, the quantifiable decreases being about 25% orgreater.
 7. The system of claim 2, wherein the second level of DBSparameters are also based on a constraint of maximizing battery life ofthe DBS device.
 8. A movement disorder therapy system comprising: amovement disorder diagnostic device comprising at least onephysiological or movement sensor adapted to be worn, attached or held atdifferent locations on the surface of the subject's body and having asignal related to a subject's motion, the movement disorder diagnosticdevice adapted to provide therapy to a subject with a deep brainstimulation (DBS) device operable with adjustable DBS parameters, and tomeasure movement data based at least in part on the signal of the atleast one sensor while the subject performs at least one movementdisorder test, the movement disorder diagnostic device furthercomprising at least one electronic component adapted to collect andtransmit the measured movement data; a processor comprising aquantification algorithm and a determination algorithm, the processoradapted to, at least in part, extract at least one kinematic featurefrom the measured movement data, the quantification algorithm adapted toreceive data corresponding to the subject's measured motor symptoms andthe at least one extracted kinematic feature and to quantify motorsymptoms of the subject based thereon, and the determination algorithmadapted to provide a suggested level of DBS parameters based on a modeof therapy or treatment corresponding to the subject's needs based atleast in part on the quantified motor symptoms; a data output comprisingdata corresponding to the subject's measured and quantified motorsymptoms and/or the suggested DBS parameters, the data output adapted tobe displayed visually for review by a clinician, physician, ortechnician to determine a second level of DBS parameters for a tuningoutput based on the data output; and the tuning output adapted tointerface with the subject's DBS device to provide the second level ofDBS parameters for the subject's DBS device to alter the subject'ssymptomatic movement and to be entered into the subject's DBS devicesuch that the subject's DBS device operates under the second level ofDBS parameters, wherein the at least one kinematic feature is selectedfrom the group consisting of peak power angular velocity, peak powerangle, RMS angular velocity, frequency, maximum amplitude, maximumpeak-to-peak amplitude, mean angular velocity, and wavelet parameters,peak power acceleration, peak power velocity, peak power position, RMSacceleration, RMS velocity, RMS position, mean acceleration, waveletparameters, covariance of any of the kinematic features, and standarddeviation over time of any of these kinematic features.
 9. The system ofclaim 8, wherein the data output is adapted to be displayed in the formof a tuning map that is a two-dimensional representation of athree-dimensional graph.
 10. The system of claim 9, wherein thesuggested level of DBS parameters corresponds to a quantifiable decreasein the severity and/or occurrence of at least one motor symptom, thequantifiable decrease being about 25% or greater.
 11. The system ofclaim 9, wherein the suggested level of DBS parameters corresponds to aquantifiable decrease in the severity and/or occurrence of at least oneside effect in the severity of at least one side effect, thequantifiable decrease being about 25% or greater.
 12. The system ofclaim 9, wherein the quantification algorithm includes and artificialneural network, a Bayesian network, and/or a genetic algorithm.
 13. Thesystem of claim 9, wherein the second level of DBS parameters are alsobased on a constraint of maximizing battery life of the DBS device. 14.A movement disorder therapy system comprising: a movement disorderdiagnostic device comprising at least one physiological or movementsensor adapted to be worn, attached or held at different locations onthe surface of the subject's body and having a signal related to asubject's motion, the movement disorder diagnostic device adapted toprovide therapy to a subject with a deep brain stimulation (DBS) deviceoperable with adjustable DBS parameters, and to measure movement databased at least in part on the signal of the at least one sensor whilethe subject performs at least one movement disorder test, the movementdisorder diagnostic device further comprising at least one electroniccomponent adapted to collect and transmit the measured movement data; aprocessor comprising a quantification algorithm and a determinationalgorithm, the processor adapted to, at least in part, extract at leastone kinematic feature from the measured movement data, thequantification algorithm adapted to receive data corresponding to thesubject's measured motor symptoms and the at least one extractedkinematic feature and to quantify motor symptoms of the subject basedthereon, and the determination algorithm adapted to provide a secondlevel of DBS parameters based on a mode of therapy or treatmentcorresponding to the subject's needs based at least in part on thequantified motor symptoms; and a tuning output adapted to interface withthe subject's DBS device to provide the second level of DBS parametersfor the subject's DBS device to alter the subject's symptomatic movementand to be automatically entered into the subject's DBS device such thatthe subject's DBS device operates under the second level of DBSparameters, wherein the quantification algorithm includes and artificialneural network, a Bayesian network, and/or a genetic algorithm.
 15. Thesystem of claim 14, further comprising a data output comprising datacorresponding to the subject's measured and quantified motor symptomsand/or the second level of DBS parameters, the data output adapted to bedisplayed visually for review by a clinician, physician, or technician.16. The system of claim 15, wherein the data output is adapted to bedisplayed in the form of a tuning map that is a two-dimensionalrepresentation of a three-dimensional graph.
 17. The system of claim 14,wherein the second level of DBS parameters corresponds to a quantifiabledecrease in the severity and/or occurrence of at least one motorsymptom, the quantifiable decreases being about 25% or greater.
 18. Thesystem of claim 14, wherein the second level of DBS parameterscorresponds to a quantifiable decrease in the severity of at least oneside effect, the quantifiable decreases being about 25% or greater. 19.The system of claim 14, wherein the second level of DBS parameterscorresponds to a quantifiable increased ability for the subject toperform at least one activity of daily living.
 20. The system of claim14, wherein the second level of DBS parameters are also based on aconstraint of maximizing battery life of the DBS device.